IL-13 signaling via IL-$ 13Rα_{2} $ triggers TGF-$ β_{1} $-dependent allograft fibrosis
Background Allograft fibrosis still remains a critical problem in transplantation, including heart transplantation. The IL-13/TGF-$ β_{1} $ interaction has previously been identified as a key pathway orchestrating fibrosis in different inflammatory immune disorders. Here we investigate if this pathw...
Ausführliche Beschreibung
Gespeichert in:
| Autor*in: |
Brunner, Stefan M [verfasserIn] Schiechl, Gabriela [verfasserIn] Kesselring, Rebecca [verfasserIn] Martin, Maria [verfasserIn] Balam, Saidou [verfasserIn] Schlitt, Hans J [verfasserIn] Geissler, Edward K [verfasserIn] Fichtner-Feigl, Stefan [verfasserIn] |
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| Format: |
E-Artikel |
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| Sprache: |
Englisch |
| Erschienen: |
2013 |
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| Schlagwörter: |
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| Übergeordnetes Werk: |
Enthalten in: Transplantation research - London : Biomed Central, 2012, 2(2013), 1 vom: 22. Okt. |
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| Übergeordnetes Werk: |
volume:2 ; year:2013 ; number:1 ; day:22 ; month:10 |
| Links: |
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| DOI / URN: |
10.1186/2047-1440-2-16 |
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| Katalog-ID: |
SPR032215622 |
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| 100 | 1 | |a Brunner, Stefan M |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a IL-13 signaling via IL-$ 13Rα_{2} $ triggers TGF-$ β_{1} $-dependent allograft fibrosis |
| 264 | 1 | |c 2013 | |
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| 520 | |a Background Allograft fibrosis still remains a critical problem in transplantation, including heart transplantation. The IL-13/TGF-$ β_{1} $ interaction has previously been identified as a key pathway orchestrating fibrosis in different inflammatory immune disorders. Here we investigate if this pathway is also responsible for allograft fibrosis and if interference with the IL-13/TGF-$ β_{1} $ interaction prevents allograft fibrosis. Methods FVB or control DBA/1 donor hearts were transplanted heterotopically into DBA/1 recipient mice and hearts were explanted at day 60 and 100 post-transplantation. Cardiac tissue was examined by Masson’s trichrome staining and immunohistochemistry for CD4, CD8, CD11b, IL-13, Fas ligand, matrix metalloproteinase (MMP)-1, MMP-13, β2-microglobulin, and Gremlin-1. Graft-infiltrating cells were isolated and analyzed by flow cytometry. IL-13 and TGF-$ β_{1} $ levels were determined by enzyme-linked immunosorbent assay (ELISA) and the amount of collagen was quantified using a Sircol assay; IL-$ 13Rα_{2} $ expression was detected by Western blotting. In some experiments IL-13/ TGF-$ β_{1} $ signaling was blocked with specific IL-$ 13Rα_{2} $ siRNA. Additionally, a PCR array of RNA isolated from the allografts was performed to analyze expression of multiple genes involved in fibrosis. Results Both groups survived long-term (>100 days). The allogeneic grafts were infiltrated by significantly increased numbers of $ CD4^{+} $ (P <0.0001), $ CD8^{+} $ (P <0.0001), and $ CD11b^{+} $ cells (P = 0.0065) by day 100. Furthermore, elevated IL-13 levels (P = 0.0003) and numbers of infiltrating IL-$ 13^{+} $ cells (P = 0.0037), together with an expression of IL-$ 13Rα_{2} $, were detected only within allografts. The expression of IL-13 and IL-$ 13Rα_{2} $ resulted in significantly increased TGF-$ β_{1} $ levels (P <0.0001), higher numbers of $ CD11b^{high} %$ Gr1^{intermediate} $TGF-$ β_{1} $+ cells, and elevated cardiac collagen deposition (P = 0.0094). The allograft fibrosis found in these experiments was accompanied by upregulation of multiple profibrotic genes, which was confirmed by immunohistochemical stainings of allograft tissue. Blockage of the IL-13/TGF-$ β_{1} $ interaction by IL-$ 13Rα_{2} $ siRNA led to lower numbers of $ CD11b^{high} %$ Gr1^{intermediate} $TGF-$ β_{1} $+, $ CD4^{+} $, $ CD8^{+} $, and $ CD11b^{+} $ cells, and prevented collagen deposition (P = 0.0018) within these allografts. Conclusions IL-13 signaling via IL-$ 13Rα_{2} $ induces TGF-$ β_{1} $ and causes allograft fibrosis in a murine model of chronic transplant rejection. Blockage of this IL-13/TGF-$ β_{1} $ interaction by IL-$ 13Rα_{2} $ siRNA prevents cardiac allograft fibrosis. Thus, IL-$ 13Rα_{2} $ may be exploitable as a future target to reduce allograft fibrosis in organ transplantation. | ||
| 650 | 4 | |a IL-13 |7 (dpeaa)DE-He213 | |
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| 650 | 4 | |a TGF-β |7 (dpeaa)DE-He213 | |
| 650 | 4 | |a Allograft fibrosis |7 (dpeaa)DE-He213 | |
| 650 | 4 | |a Heart transplantation |7 (dpeaa)DE-He213 | |
| 700 | 1 | |a Schiechl, Gabriela |e verfasserin |4 aut | |
| 700 | 1 | |a Kesselring, Rebecca |e verfasserin |4 aut | |
| 700 | 1 | |a Martin, Maria |e verfasserin |4 aut | |
| 700 | 1 | |a Balam, Saidou |e verfasserin |4 aut | |
| 700 | 1 | |a Schlitt, Hans J |e verfasserin |4 aut | |
| 700 | 1 | |a Geissler, Edward K |e verfasserin |4 aut | |
| 700 | 1 | |a Fichtner-Feigl, Stefan |e verfasserin |4 aut | |
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10.1186/2047-1440-2-16 doi (DE-627)SPR032215622 (SPR)2047-1440-2-16-e DE-627 ger DE-627 rakwb eng 610 ASE Brunner, Stefan M verfasserin aut IL-13 signaling via IL-$ 13Rα_{2} $ triggers TGF-$ β_{1} $-dependent allograft fibrosis 2013 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Background Allograft fibrosis still remains a critical problem in transplantation, including heart transplantation. The IL-13/TGF-$ β_{1} $ interaction has previously been identified as a key pathway orchestrating fibrosis in different inflammatory immune disorders. Here we investigate if this pathway is also responsible for allograft fibrosis and if interference with the IL-13/TGF-$ β_{1} $ interaction prevents allograft fibrosis. Methods FVB or control DBA/1 donor hearts were transplanted heterotopically into DBA/1 recipient mice and hearts were explanted at day 60 and 100 post-transplantation. Cardiac tissue was examined by Masson’s trichrome staining and immunohistochemistry for CD4, CD8, CD11b, IL-13, Fas ligand, matrix metalloproteinase (MMP)-1, MMP-13, β2-microglobulin, and Gremlin-1. Graft-infiltrating cells were isolated and analyzed by flow cytometry. IL-13 and TGF-$ β_{1} $ levels were determined by enzyme-linked immunosorbent assay (ELISA) and the amount of collagen was quantified using a Sircol assay; IL-$ 13Rα_{2} $ expression was detected by Western blotting. In some experiments IL-13/ TGF-$ β_{1} $ signaling was blocked with specific IL-$ 13Rα_{2} $ siRNA. Additionally, a PCR array of RNA isolated from the allografts was performed to analyze expression of multiple genes involved in fibrosis. Results Both groups survived long-term (>100 days). The allogeneic grafts were infiltrated by significantly increased numbers of $ CD4^{+} $ (P <0.0001), $ CD8^{+} $ (P <0.0001), and $ CD11b^{+} $ cells (P = 0.0065) by day 100. Furthermore, elevated IL-13 levels (P = 0.0003) and numbers of infiltrating IL-$ 13^{+} $ cells (P = 0.0037), together with an expression of IL-$ 13Rα_{2} $, were detected only within allografts. The expression of IL-13 and IL-$ 13Rα_{2} $ resulted in significantly increased TGF-$ β_{1} $ levels (P <0.0001), higher numbers of $ CD11b^{high} %$ Gr1^{intermediate} $TGF-$ β_{1} $+ cells, and elevated cardiac collagen deposition (P = 0.0094). The allograft fibrosis found in these experiments was accompanied by upregulation of multiple profibrotic genes, which was confirmed by immunohistochemical stainings of allograft tissue. Blockage of the IL-13/TGF-$ β_{1} $ interaction by IL-$ 13Rα_{2} $ siRNA led to lower numbers of $ CD11b^{high} %$ Gr1^{intermediate} $TGF-$ β_{1} $+, $ CD4^{+} $, $ CD8^{+} $, and $ CD11b^{+} $ cells, and prevented collagen deposition (P = 0.0018) within these allografts. Conclusions IL-13 signaling via IL-$ 13Rα_{2} $ induces TGF-$ β_{1} $ and causes allograft fibrosis in a murine model of chronic transplant rejection. Blockage of this IL-13/TGF-$ β_{1} $ interaction by IL-$ 13Rα_{2} $ siRNA prevents cardiac allograft fibrosis. Thus, IL-$ 13Rα_{2} $ may be exploitable as a future target to reduce allograft fibrosis in organ transplantation. IL-13 (dpeaa)DE-He213 IL-13Rα (dpeaa)DE-He213 TGF-β (dpeaa)DE-He213 Allograft fibrosis (dpeaa)DE-He213 Heart transplantation (dpeaa)DE-He213 Schiechl, Gabriela verfasserin aut Kesselring, Rebecca verfasserin aut Martin, Maria verfasserin aut Balam, Saidou verfasserin aut Schlitt, Hans J verfasserin aut Geissler, Edward K verfasserin aut Fichtner-Feigl, Stefan verfasserin aut Enthalten in Transplantation research London : Biomed Central, 2012 2(2013), 1 vom: 22. Okt. (DE-627)718830733 (DE-600)2668672-7 2047-1440 nnns volume:2 year:2013 number:1 day:22 month:10 https://dx.doi.org/10.1186/2047-1440-2-16 kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 2 2013 1 22 10 |
| spelling |
10.1186/2047-1440-2-16 doi (DE-627)SPR032215622 (SPR)2047-1440-2-16-e DE-627 ger DE-627 rakwb eng 610 ASE Brunner, Stefan M verfasserin aut IL-13 signaling via IL-$ 13Rα_{2} $ triggers TGF-$ β_{1} $-dependent allograft fibrosis 2013 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Background Allograft fibrosis still remains a critical problem in transplantation, including heart transplantation. The IL-13/TGF-$ β_{1} $ interaction has previously been identified as a key pathway orchestrating fibrosis in different inflammatory immune disorders. Here we investigate if this pathway is also responsible for allograft fibrosis and if interference with the IL-13/TGF-$ β_{1} $ interaction prevents allograft fibrosis. Methods FVB or control DBA/1 donor hearts were transplanted heterotopically into DBA/1 recipient mice and hearts were explanted at day 60 and 100 post-transplantation. Cardiac tissue was examined by Masson’s trichrome staining and immunohistochemistry for CD4, CD8, CD11b, IL-13, Fas ligand, matrix metalloproteinase (MMP)-1, MMP-13, β2-microglobulin, and Gremlin-1. Graft-infiltrating cells were isolated and analyzed by flow cytometry. IL-13 and TGF-$ β_{1} $ levels were determined by enzyme-linked immunosorbent assay (ELISA) and the amount of collagen was quantified using a Sircol assay; IL-$ 13Rα_{2} $ expression was detected by Western blotting. In some experiments IL-13/ TGF-$ β_{1} $ signaling was blocked with specific IL-$ 13Rα_{2} $ siRNA. Additionally, a PCR array of RNA isolated from the allografts was performed to analyze expression of multiple genes involved in fibrosis. Results Both groups survived long-term (>100 days). The allogeneic grafts were infiltrated by significantly increased numbers of $ CD4^{+} $ (P <0.0001), $ CD8^{+} $ (P <0.0001), and $ CD11b^{+} $ cells (P = 0.0065) by day 100. Furthermore, elevated IL-13 levels (P = 0.0003) and numbers of infiltrating IL-$ 13^{+} $ cells (P = 0.0037), together with an expression of IL-$ 13Rα_{2} $, were detected only within allografts. The expression of IL-13 and IL-$ 13Rα_{2} $ resulted in significantly increased TGF-$ β_{1} $ levels (P <0.0001), higher numbers of $ CD11b^{high} %$ Gr1^{intermediate} $TGF-$ β_{1} $+ cells, and elevated cardiac collagen deposition (P = 0.0094). The allograft fibrosis found in these experiments was accompanied by upregulation of multiple profibrotic genes, which was confirmed by immunohistochemical stainings of allograft tissue. Blockage of the IL-13/TGF-$ β_{1} $ interaction by IL-$ 13Rα_{2} $ siRNA led to lower numbers of $ CD11b^{high} %$ Gr1^{intermediate} $TGF-$ β_{1} $+, $ CD4^{+} $, $ CD8^{+} $, and $ CD11b^{+} $ cells, and prevented collagen deposition (P = 0.0018) within these allografts. Conclusions IL-13 signaling via IL-$ 13Rα_{2} $ induces TGF-$ β_{1} $ and causes allograft fibrosis in a murine model of chronic transplant rejection. Blockage of this IL-13/TGF-$ β_{1} $ interaction by IL-$ 13Rα_{2} $ siRNA prevents cardiac allograft fibrosis. Thus, IL-$ 13Rα_{2} $ may be exploitable as a future target to reduce allograft fibrosis in organ transplantation. IL-13 (dpeaa)DE-He213 IL-13Rα (dpeaa)DE-He213 TGF-β (dpeaa)DE-He213 Allograft fibrosis (dpeaa)DE-He213 Heart transplantation (dpeaa)DE-He213 Schiechl, Gabriela verfasserin aut Kesselring, Rebecca verfasserin aut Martin, Maria verfasserin aut Balam, Saidou verfasserin aut Schlitt, Hans J verfasserin aut Geissler, Edward K verfasserin aut Fichtner-Feigl, Stefan verfasserin aut Enthalten in Transplantation research London : Biomed Central, 2012 2(2013), 1 vom: 22. Okt. (DE-627)718830733 (DE-600)2668672-7 2047-1440 nnns volume:2 year:2013 number:1 day:22 month:10 https://dx.doi.org/10.1186/2047-1440-2-16 kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 2 2013 1 22 10 |
| allfields_unstemmed |
10.1186/2047-1440-2-16 doi (DE-627)SPR032215622 (SPR)2047-1440-2-16-e DE-627 ger DE-627 rakwb eng 610 ASE Brunner, Stefan M verfasserin aut IL-13 signaling via IL-$ 13Rα_{2} $ triggers TGF-$ β_{1} $-dependent allograft fibrosis 2013 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Background Allograft fibrosis still remains a critical problem in transplantation, including heart transplantation. The IL-13/TGF-$ β_{1} $ interaction has previously been identified as a key pathway orchestrating fibrosis in different inflammatory immune disorders. Here we investigate if this pathway is also responsible for allograft fibrosis and if interference with the IL-13/TGF-$ β_{1} $ interaction prevents allograft fibrosis. Methods FVB or control DBA/1 donor hearts were transplanted heterotopically into DBA/1 recipient mice and hearts were explanted at day 60 and 100 post-transplantation. Cardiac tissue was examined by Masson’s trichrome staining and immunohistochemistry for CD4, CD8, CD11b, IL-13, Fas ligand, matrix metalloproteinase (MMP)-1, MMP-13, β2-microglobulin, and Gremlin-1. Graft-infiltrating cells were isolated and analyzed by flow cytometry. IL-13 and TGF-$ β_{1} $ levels were determined by enzyme-linked immunosorbent assay (ELISA) and the amount of collagen was quantified using a Sircol assay; IL-$ 13Rα_{2} $ expression was detected by Western blotting. In some experiments IL-13/ TGF-$ β_{1} $ signaling was blocked with specific IL-$ 13Rα_{2} $ siRNA. Additionally, a PCR array of RNA isolated from the allografts was performed to analyze expression of multiple genes involved in fibrosis. Results Both groups survived long-term (>100 days). The allogeneic grafts were infiltrated by significantly increased numbers of $ CD4^{+} $ (P <0.0001), $ CD8^{+} $ (P <0.0001), and $ CD11b^{+} $ cells (P = 0.0065) by day 100. Furthermore, elevated IL-13 levels (P = 0.0003) and numbers of infiltrating IL-$ 13^{+} $ cells (P = 0.0037), together with an expression of IL-$ 13Rα_{2} $, were detected only within allografts. The expression of IL-13 and IL-$ 13Rα_{2} $ resulted in significantly increased TGF-$ β_{1} $ levels (P <0.0001), higher numbers of $ CD11b^{high} %$ Gr1^{intermediate} $TGF-$ β_{1} $+ cells, and elevated cardiac collagen deposition (P = 0.0094). The allograft fibrosis found in these experiments was accompanied by upregulation of multiple profibrotic genes, which was confirmed by immunohistochemical stainings of allograft tissue. Blockage of the IL-13/TGF-$ β_{1} $ interaction by IL-$ 13Rα_{2} $ siRNA led to lower numbers of $ CD11b^{high} %$ Gr1^{intermediate} $TGF-$ β_{1} $+, $ CD4^{+} $, $ CD8^{+} $, and $ CD11b^{+} $ cells, and prevented collagen deposition (P = 0.0018) within these allografts. Conclusions IL-13 signaling via IL-$ 13Rα_{2} $ induces TGF-$ β_{1} $ and causes allograft fibrosis in a murine model of chronic transplant rejection. Blockage of this IL-13/TGF-$ β_{1} $ interaction by IL-$ 13Rα_{2} $ siRNA prevents cardiac allograft fibrosis. Thus, IL-$ 13Rα_{2} $ may be exploitable as a future target to reduce allograft fibrosis in organ transplantation. IL-13 (dpeaa)DE-He213 IL-13Rα (dpeaa)DE-He213 TGF-β (dpeaa)DE-He213 Allograft fibrosis (dpeaa)DE-He213 Heart transplantation (dpeaa)DE-He213 Schiechl, Gabriela verfasserin aut Kesselring, Rebecca verfasserin aut Martin, Maria verfasserin aut Balam, Saidou verfasserin aut Schlitt, Hans J verfasserin aut Geissler, Edward K verfasserin aut Fichtner-Feigl, Stefan verfasserin aut Enthalten in Transplantation research London : Biomed Central, 2012 2(2013), 1 vom: 22. Okt. (DE-627)718830733 (DE-600)2668672-7 2047-1440 nnns volume:2 year:2013 number:1 day:22 month:10 https://dx.doi.org/10.1186/2047-1440-2-16 kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 2 2013 1 22 10 |
| allfieldsGer |
10.1186/2047-1440-2-16 doi (DE-627)SPR032215622 (SPR)2047-1440-2-16-e DE-627 ger DE-627 rakwb eng 610 ASE Brunner, Stefan M verfasserin aut IL-13 signaling via IL-$ 13Rα_{2} $ triggers TGF-$ β_{1} $-dependent allograft fibrosis 2013 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Background Allograft fibrosis still remains a critical problem in transplantation, including heart transplantation. The IL-13/TGF-$ β_{1} $ interaction has previously been identified as a key pathway orchestrating fibrosis in different inflammatory immune disorders. Here we investigate if this pathway is also responsible for allograft fibrosis and if interference with the IL-13/TGF-$ β_{1} $ interaction prevents allograft fibrosis. Methods FVB or control DBA/1 donor hearts were transplanted heterotopically into DBA/1 recipient mice and hearts were explanted at day 60 and 100 post-transplantation. Cardiac tissue was examined by Masson’s trichrome staining and immunohistochemistry for CD4, CD8, CD11b, IL-13, Fas ligand, matrix metalloproteinase (MMP)-1, MMP-13, β2-microglobulin, and Gremlin-1. Graft-infiltrating cells were isolated and analyzed by flow cytometry. IL-13 and TGF-$ β_{1} $ levels were determined by enzyme-linked immunosorbent assay (ELISA) and the amount of collagen was quantified using a Sircol assay; IL-$ 13Rα_{2} $ expression was detected by Western blotting. In some experiments IL-13/ TGF-$ β_{1} $ signaling was blocked with specific IL-$ 13Rα_{2} $ siRNA. Additionally, a PCR array of RNA isolated from the allografts was performed to analyze expression of multiple genes involved in fibrosis. Results Both groups survived long-term (>100 days). The allogeneic grafts were infiltrated by significantly increased numbers of $ CD4^{+} $ (P <0.0001), $ CD8^{+} $ (P <0.0001), and $ CD11b^{+} $ cells (P = 0.0065) by day 100. Furthermore, elevated IL-13 levels (P = 0.0003) and numbers of infiltrating IL-$ 13^{+} $ cells (P = 0.0037), together with an expression of IL-$ 13Rα_{2} $, were detected only within allografts. The expression of IL-13 and IL-$ 13Rα_{2} $ resulted in significantly increased TGF-$ β_{1} $ levels (P <0.0001), higher numbers of $ CD11b^{high} %$ Gr1^{intermediate} $TGF-$ β_{1} $+ cells, and elevated cardiac collagen deposition (P = 0.0094). The allograft fibrosis found in these experiments was accompanied by upregulation of multiple profibrotic genes, which was confirmed by immunohistochemical stainings of allograft tissue. Blockage of the IL-13/TGF-$ β_{1} $ interaction by IL-$ 13Rα_{2} $ siRNA led to lower numbers of $ CD11b^{high} %$ Gr1^{intermediate} $TGF-$ β_{1} $+, $ CD4^{+} $, $ CD8^{+} $, and $ CD11b^{+} $ cells, and prevented collagen deposition (P = 0.0018) within these allografts. Conclusions IL-13 signaling via IL-$ 13Rα_{2} $ induces TGF-$ β_{1} $ and causes allograft fibrosis in a murine model of chronic transplant rejection. Blockage of this IL-13/TGF-$ β_{1} $ interaction by IL-$ 13Rα_{2} $ siRNA prevents cardiac allograft fibrosis. Thus, IL-$ 13Rα_{2} $ may be exploitable as a future target to reduce allograft fibrosis in organ transplantation. IL-13 (dpeaa)DE-He213 IL-13Rα (dpeaa)DE-He213 TGF-β (dpeaa)DE-He213 Allograft fibrosis (dpeaa)DE-He213 Heart transplantation (dpeaa)DE-He213 Schiechl, Gabriela verfasserin aut Kesselring, Rebecca verfasserin aut Martin, Maria verfasserin aut Balam, Saidou verfasserin aut Schlitt, Hans J verfasserin aut Geissler, Edward K verfasserin aut Fichtner-Feigl, Stefan verfasserin aut Enthalten in Transplantation research London : Biomed Central, 2012 2(2013), 1 vom: 22. Okt. (DE-627)718830733 (DE-600)2668672-7 2047-1440 nnns volume:2 year:2013 number:1 day:22 month:10 https://dx.doi.org/10.1186/2047-1440-2-16 kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 2 2013 1 22 10 |
| allfieldsSound |
10.1186/2047-1440-2-16 doi (DE-627)SPR032215622 (SPR)2047-1440-2-16-e DE-627 ger DE-627 rakwb eng 610 ASE Brunner, Stefan M verfasserin aut IL-13 signaling via IL-$ 13Rα_{2} $ triggers TGF-$ β_{1} $-dependent allograft fibrosis 2013 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Background Allograft fibrosis still remains a critical problem in transplantation, including heart transplantation. The IL-13/TGF-$ β_{1} $ interaction has previously been identified as a key pathway orchestrating fibrosis in different inflammatory immune disorders. Here we investigate if this pathway is also responsible for allograft fibrosis and if interference with the IL-13/TGF-$ β_{1} $ interaction prevents allograft fibrosis. Methods FVB or control DBA/1 donor hearts were transplanted heterotopically into DBA/1 recipient mice and hearts were explanted at day 60 and 100 post-transplantation. Cardiac tissue was examined by Masson’s trichrome staining and immunohistochemistry for CD4, CD8, CD11b, IL-13, Fas ligand, matrix metalloproteinase (MMP)-1, MMP-13, β2-microglobulin, and Gremlin-1. Graft-infiltrating cells were isolated and analyzed by flow cytometry. IL-13 and TGF-$ β_{1} $ levels were determined by enzyme-linked immunosorbent assay (ELISA) and the amount of collagen was quantified using a Sircol assay; IL-$ 13Rα_{2} $ expression was detected by Western blotting. In some experiments IL-13/ TGF-$ β_{1} $ signaling was blocked with specific IL-$ 13Rα_{2} $ siRNA. Additionally, a PCR array of RNA isolated from the allografts was performed to analyze expression of multiple genes involved in fibrosis. Results Both groups survived long-term (>100 days). The allogeneic grafts were infiltrated by significantly increased numbers of $ CD4^{+} $ (P <0.0001), $ CD8^{+} $ (P <0.0001), and $ CD11b^{+} $ cells (P = 0.0065) by day 100. Furthermore, elevated IL-13 levels (P = 0.0003) and numbers of infiltrating IL-$ 13^{+} $ cells (P = 0.0037), together with an expression of IL-$ 13Rα_{2} $, were detected only within allografts. The expression of IL-13 and IL-$ 13Rα_{2} $ resulted in significantly increased TGF-$ β_{1} $ levels (P <0.0001), higher numbers of $ CD11b^{high} %$ Gr1^{intermediate} $TGF-$ β_{1} $+ cells, and elevated cardiac collagen deposition (P = 0.0094). The allograft fibrosis found in these experiments was accompanied by upregulation of multiple profibrotic genes, which was confirmed by immunohistochemical stainings of allograft tissue. Blockage of the IL-13/TGF-$ β_{1} $ interaction by IL-$ 13Rα_{2} $ siRNA led to lower numbers of $ CD11b^{high} %$ Gr1^{intermediate} $TGF-$ β_{1} $+, $ CD4^{+} $, $ CD8^{+} $, and $ CD11b^{+} $ cells, and prevented collagen deposition (P = 0.0018) within these allografts. Conclusions IL-13 signaling via IL-$ 13Rα_{2} $ induces TGF-$ β_{1} $ and causes allograft fibrosis in a murine model of chronic transplant rejection. Blockage of this IL-13/TGF-$ β_{1} $ interaction by IL-$ 13Rα_{2} $ siRNA prevents cardiac allograft fibrosis. Thus, IL-$ 13Rα_{2} $ may be exploitable as a future target to reduce allograft fibrosis in organ transplantation. IL-13 (dpeaa)DE-He213 IL-13Rα (dpeaa)DE-He213 TGF-β (dpeaa)DE-He213 Allograft fibrosis (dpeaa)DE-He213 Heart transplantation (dpeaa)DE-He213 Schiechl, Gabriela verfasserin aut Kesselring, Rebecca verfasserin aut Martin, Maria verfasserin aut Balam, Saidou verfasserin aut Schlitt, Hans J verfasserin aut Geissler, Edward K verfasserin aut Fichtner-Feigl, Stefan verfasserin aut Enthalten in Transplantation research London : Biomed Central, 2012 2(2013), 1 vom: 22. Okt. (DE-627)718830733 (DE-600)2668672-7 2047-1440 nnns volume:2 year:2013 number:1 day:22 month:10 https://dx.doi.org/10.1186/2047-1440-2-16 kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 2 2013 1 22 10 |
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English |
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Enthalten in Transplantation research 2(2013), 1 vom: 22. Okt. volume:2 year:2013 number:1 day:22 month:10 |
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Enthalten in Transplantation research 2(2013), 1 vom: 22. Okt. volume:2 year:2013 number:1 day:22 month:10 |
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IL-13 IL-13Rα TGF-β Allograft fibrosis Heart transplantation |
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Brunner, Stefan M @@aut@@ Schiechl, Gabriela @@aut@@ Kesselring, Rebecca @@aut@@ Martin, Maria @@aut@@ Balam, Saidou @@aut@@ Schlitt, Hans J @@aut@@ Geissler, Edward K @@aut@@ Fichtner-Feigl, Stefan @@aut@@ |
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2013-10-22T00:00:00Z |
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The IL-13/TGF-$ β_{1} $ interaction has previously been identified as a key pathway orchestrating fibrosis in different inflammatory immune disorders. Here we investigate if this pathway is also responsible for allograft fibrosis and if interference with the IL-13/TGF-$ β_{1} $ interaction prevents allograft fibrosis. Methods FVB or control DBA/1 donor hearts were transplanted heterotopically into DBA/1 recipient mice and hearts were explanted at day 60 and 100 post-transplantation. Cardiac tissue was examined by Masson’s trichrome staining and immunohistochemistry for CD4, CD8, CD11b, IL-13, Fas ligand, matrix metalloproteinase (MMP)-1, MMP-13, β2-microglobulin, and Gremlin-1. Graft-infiltrating cells were isolated and analyzed by flow cytometry. IL-13 and TGF-$ β_{1} $ levels were determined by enzyme-linked immunosorbent assay (ELISA) and the amount of collagen was quantified using a Sircol assay; IL-$ 13Rα_{2} $ expression was detected by Western blotting. In some experiments IL-13/ TGF-$ β_{1} $ signaling was blocked with specific IL-$ 13Rα_{2} $ siRNA. Additionally, a PCR array of RNA isolated from the allografts was performed to analyze expression of multiple genes involved in fibrosis. Results Both groups survived long-term (>100 days). The allogeneic grafts were infiltrated by significantly increased numbers of $ CD4^{+} $ (P <0.0001), $ CD8^{+} $ (P <0.0001), and $ CD11b^{+} $ cells (P = 0.0065) by day 100. Furthermore, elevated IL-13 levels (P = 0.0003) and numbers of infiltrating IL-$ 13^{+} $ cells (P = 0.0037), together with an expression of IL-$ 13Rα_{2} $, were detected only within allografts. The expression of IL-13 and IL-$ 13Rα_{2} $ resulted in significantly increased TGF-$ β_{1} $ levels (P <0.0001), higher numbers of $ CD11b^{high} %$ Gr1^{intermediate} $TGF-$ β_{1} $+ cells, and elevated cardiac collagen deposition (P = 0.0094). The allograft fibrosis found in these experiments was accompanied by upregulation of multiple profibrotic genes, which was confirmed by immunohistochemical stainings of allograft tissue. Blockage of the IL-13/TGF-$ β_{1} $ interaction by IL-$ 13Rα_{2} $ siRNA led to lower numbers of $ CD11b^{high} %$ Gr1^{intermediate} $TGF-$ β_{1} $+, $ CD4^{+} $, $ CD8^{+} $, and $ CD11b^{+} $ cells, and prevented collagen deposition (P = 0.0018) within these allografts. Conclusions IL-13 signaling via IL-$ 13Rα_{2} $ induces TGF-$ β_{1} $ and causes allograft fibrosis in a murine model of chronic transplant rejection. Blockage of this IL-13/TGF-$ β_{1} $ interaction by IL-$ 13Rα_{2} $ siRNA prevents cardiac allograft fibrosis. 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Brunner, Stefan M |
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Brunner, Stefan M ddc 610 misc IL-13 misc IL-13Rα misc TGF-β misc Allograft fibrosis misc Heart transplantation IL-13 signaling via IL-$ 13Rα_{2} $ triggers TGF-$ β_{1} $-dependent allograft fibrosis |
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610 ASE IL-13 signaling via IL-$ 13Rα_{2} $ triggers TGF-$ β_{1} $-dependent allograft fibrosis IL-13 (dpeaa)DE-He213 IL-13Rα (dpeaa)DE-He213 TGF-β (dpeaa)DE-He213 Allograft fibrosis (dpeaa)DE-He213 Heart transplantation (dpeaa)DE-He213 |
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IL-13 signaling via IL-$ 13Rα_{2} $ triggers TGF-$ β_{1} $-dependent allograft fibrosis |
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IL-13 signaling via IL-$ 13Rα_{2} $ triggers TGF-$ β_{1} $-dependent allograft fibrosis |
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Brunner, Stefan M Schiechl, Gabriela Kesselring, Rebecca Martin, Maria Balam, Saidou Schlitt, Hans J Geissler, Edward K Fichtner-Feigl, Stefan |
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il-13 signaling via il-$ 13rα_{2} $ triggers tgf-$ β_{1} $-dependent allograft fibrosis |
| title_auth |
IL-13 signaling via IL-$ 13Rα_{2} $ triggers TGF-$ β_{1} $-dependent allograft fibrosis |
| abstract |
Background Allograft fibrosis still remains a critical problem in transplantation, including heart transplantation. The IL-13/TGF-$ β_{1} $ interaction has previously been identified as a key pathway orchestrating fibrosis in different inflammatory immune disorders. Here we investigate if this pathway is also responsible for allograft fibrosis and if interference with the IL-13/TGF-$ β_{1} $ interaction prevents allograft fibrosis. Methods FVB or control DBA/1 donor hearts were transplanted heterotopically into DBA/1 recipient mice and hearts were explanted at day 60 and 100 post-transplantation. Cardiac tissue was examined by Masson’s trichrome staining and immunohistochemistry for CD4, CD8, CD11b, IL-13, Fas ligand, matrix metalloproteinase (MMP)-1, MMP-13, β2-microglobulin, and Gremlin-1. Graft-infiltrating cells were isolated and analyzed by flow cytometry. IL-13 and TGF-$ β_{1} $ levels were determined by enzyme-linked immunosorbent assay (ELISA) and the amount of collagen was quantified using a Sircol assay; IL-$ 13Rα_{2} $ expression was detected by Western blotting. In some experiments IL-13/ TGF-$ β_{1} $ signaling was blocked with specific IL-$ 13Rα_{2} $ siRNA. Additionally, a PCR array of RNA isolated from the allografts was performed to analyze expression of multiple genes involved in fibrosis. Results Both groups survived long-term (>100 days). The allogeneic grafts were infiltrated by significantly increased numbers of $ CD4^{+} $ (P <0.0001), $ CD8^{+} $ (P <0.0001), and $ CD11b^{+} $ cells (P = 0.0065) by day 100. Furthermore, elevated IL-13 levels (P = 0.0003) and numbers of infiltrating IL-$ 13^{+} $ cells (P = 0.0037), together with an expression of IL-$ 13Rα_{2} $, were detected only within allografts. The expression of IL-13 and IL-$ 13Rα_{2} $ resulted in significantly increased TGF-$ β_{1} $ levels (P <0.0001), higher numbers of $ CD11b^{high} %$ Gr1^{intermediate} $TGF-$ β_{1} $+ cells, and elevated cardiac collagen deposition (P = 0.0094). The allograft fibrosis found in these experiments was accompanied by upregulation of multiple profibrotic genes, which was confirmed by immunohistochemical stainings of allograft tissue. Blockage of the IL-13/TGF-$ β_{1} $ interaction by IL-$ 13Rα_{2} $ siRNA led to lower numbers of $ CD11b^{high} %$ Gr1^{intermediate} $TGF-$ β_{1} $+, $ CD4^{+} $, $ CD8^{+} $, and $ CD11b^{+} $ cells, and prevented collagen deposition (P = 0.0018) within these allografts. Conclusions IL-13 signaling via IL-$ 13Rα_{2} $ induces TGF-$ β_{1} $ and causes allograft fibrosis in a murine model of chronic transplant rejection. Blockage of this IL-13/TGF-$ β_{1} $ interaction by IL-$ 13Rα_{2} $ siRNA prevents cardiac allograft fibrosis. Thus, IL-$ 13Rα_{2} $ may be exploitable as a future target to reduce allograft fibrosis in organ transplantation. |
| abstractGer |
Background Allograft fibrosis still remains a critical problem in transplantation, including heart transplantation. The IL-13/TGF-$ β_{1} $ interaction has previously been identified as a key pathway orchestrating fibrosis in different inflammatory immune disorders. Here we investigate if this pathway is also responsible for allograft fibrosis and if interference with the IL-13/TGF-$ β_{1} $ interaction prevents allograft fibrosis. Methods FVB or control DBA/1 donor hearts were transplanted heterotopically into DBA/1 recipient mice and hearts were explanted at day 60 and 100 post-transplantation. Cardiac tissue was examined by Masson’s trichrome staining and immunohistochemistry for CD4, CD8, CD11b, IL-13, Fas ligand, matrix metalloproteinase (MMP)-1, MMP-13, β2-microglobulin, and Gremlin-1. Graft-infiltrating cells were isolated and analyzed by flow cytometry. IL-13 and TGF-$ β_{1} $ levels were determined by enzyme-linked immunosorbent assay (ELISA) and the amount of collagen was quantified using a Sircol assay; IL-$ 13Rα_{2} $ expression was detected by Western blotting. In some experiments IL-13/ TGF-$ β_{1} $ signaling was blocked with specific IL-$ 13Rα_{2} $ siRNA. Additionally, a PCR array of RNA isolated from the allografts was performed to analyze expression of multiple genes involved in fibrosis. Results Both groups survived long-term (>100 days). The allogeneic grafts were infiltrated by significantly increased numbers of $ CD4^{+} $ (P <0.0001), $ CD8^{+} $ (P <0.0001), and $ CD11b^{+} $ cells (P = 0.0065) by day 100. Furthermore, elevated IL-13 levels (P = 0.0003) and numbers of infiltrating IL-$ 13^{+} $ cells (P = 0.0037), together with an expression of IL-$ 13Rα_{2} $, were detected only within allografts. The expression of IL-13 and IL-$ 13Rα_{2} $ resulted in significantly increased TGF-$ β_{1} $ levels (P <0.0001), higher numbers of $ CD11b^{high} %$ Gr1^{intermediate} $TGF-$ β_{1} $+ cells, and elevated cardiac collagen deposition (P = 0.0094). The allograft fibrosis found in these experiments was accompanied by upregulation of multiple profibrotic genes, which was confirmed by immunohistochemical stainings of allograft tissue. Blockage of the IL-13/TGF-$ β_{1} $ interaction by IL-$ 13Rα_{2} $ siRNA led to lower numbers of $ CD11b^{high} %$ Gr1^{intermediate} $TGF-$ β_{1} $+, $ CD4^{+} $, $ CD8^{+} $, and $ CD11b^{+} $ cells, and prevented collagen deposition (P = 0.0018) within these allografts. Conclusions IL-13 signaling via IL-$ 13Rα_{2} $ induces TGF-$ β_{1} $ and causes allograft fibrosis in a murine model of chronic transplant rejection. Blockage of this IL-13/TGF-$ β_{1} $ interaction by IL-$ 13Rα_{2} $ siRNA prevents cardiac allograft fibrosis. Thus, IL-$ 13Rα_{2} $ may be exploitable as a future target to reduce allograft fibrosis in organ transplantation. |
| abstract_unstemmed |
Background Allograft fibrosis still remains a critical problem in transplantation, including heart transplantation. The IL-13/TGF-$ β_{1} $ interaction has previously been identified as a key pathway orchestrating fibrosis in different inflammatory immune disorders. Here we investigate if this pathway is also responsible for allograft fibrosis and if interference with the IL-13/TGF-$ β_{1} $ interaction prevents allograft fibrosis. Methods FVB or control DBA/1 donor hearts were transplanted heterotopically into DBA/1 recipient mice and hearts were explanted at day 60 and 100 post-transplantation. Cardiac tissue was examined by Masson’s trichrome staining and immunohistochemistry for CD4, CD8, CD11b, IL-13, Fas ligand, matrix metalloproteinase (MMP)-1, MMP-13, β2-microglobulin, and Gremlin-1. Graft-infiltrating cells were isolated and analyzed by flow cytometry. IL-13 and TGF-$ β_{1} $ levels were determined by enzyme-linked immunosorbent assay (ELISA) and the amount of collagen was quantified using a Sircol assay; IL-$ 13Rα_{2} $ expression was detected by Western blotting. In some experiments IL-13/ TGF-$ β_{1} $ signaling was blocked with specific IL-$ 13Rα_{2} $ siRNA. Additionally, a PCR array of RNA isolated from the allografts was performed to analyze expression of multiple genes involved in fibrosis. Results Both groups survived long-term (>100 days). The allogeneic grafts were infiltrated by significantly increased numbers of $ CD4^{+} $ (P <0.0001), $ CD8^{+} $ (P <0.0001), and $ CD11b^{+} $ cells (P = 0.0065) by day 100. Furthermore, elevated IL-13 levels (P = 0.0003) and numbers of infiltrating IL-$ 13^{+} $ cells (P = 0.0037), together with an expression of IL-$ 13Rα_{2} $, were detected only within allografts. The expression of IL-13 and IL-$ 13Rα_{2} $ resulted in significantly increased TGF-$ β_{1} $ levels (P <0.0001), higher numbers of $ CD11b^{high} %$ Gr1^{intermediate} $TGF-$ β_{1} $+ cells, and elevated cardiac collagen deposition (P = 0.0094). The allograft fibrosis found in these experiments was accompanied by upregulation of multiple profibrotic genes, which was confirmed by immunohistochemical stainings of allograft tissue. Blockage of the IL-13/TGF-$ β_{1} $ interaction by IL-$ 13Rα_{2} $ siRNA led to lower numbers of $ CD11b^{high} %$ Gr1^{intermediate} $TGF-$ β_{1} $+, $ CD4^{+} $, $ CD8^{+} $, and $ CD11b^{+} $ cells, and prevented collagen deposition (P = 0.0018) within these allografts. Conclusions IL-13 signaling via IL-$ 13Rα_{2} $ induces TGF-$ β_{1} $ and causes allograft fibrosis in a murine model of chronic transplant rejection. Blockage of this IL-13/TGF-$ β_{1} $ interaction by IL-$ 13Rα_{2} $ siRNA prevents cardiac allograft fibrosis. Thus, IL-$ 13Rα_{2} $ may be exploitable as a future target to reduce allograft fibrosis in organ transplantation. |
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The IL-13/TGF-$ β_{1} $ interaction has previously been identified as a key pathway orchestrating fibrosis in different inflammatory immune disorders. Here we investigate if this pathway is also responsible for allograft fibrosis and if interference with the IL-13/TGF-$ β_{1} $ interaction prevents allograft fibrosis. Methods FVB or control DBA/1 donor hearts were transplanted heterotopically into DBA/1 recipient mice and hearts were explanted at day 60 and 100 post-transplantation. Cardiac tissue was examined by Masson’s trichrome staining and immunohistochemistry for CD4, CD8, CD11b, IL-13, Fas ligand, matrix metalloproteinase (MMP)-1, MMP-13, β2-microglobulin, and Gremlin-1. Graft-infiltrating cells were isolated and analyzed by flow cytometry. IL-13 and TGF-$ β_{1} $ levels were determined by enzyme-linked immunosorbent assay (ELISA) and the amount of collagen was quantified using a Sircol assay; IL-$ 13Rα_{2} $ expression was detected by Western blotting. In some experiments IL-13/ TGF-$ β_{1} $ signaling was blocked with specific IL-$ 13Rα_{2} $ siRNA. Additionally, a PCR array of RNA isolated from the allografts was performed to analyze expression of multiple genes involved in fibrosis. Results Both groups survived long-term (>100 days). The allogeneic grafts were infiltrated by significantly increased numbers of $ CD4^{+} $ (P <0.0001), $ CD8^{+} $ (P <0.0001), and $ CD11b^{+} $ cells (P = 0.0065) by day 100. Furthermore, elevated IL-13 levels (P = 0.0003) and numbers of infiltrating IL-$ 13^{+} $ cells (P = 0.0037), together with an expression of IL-$ 13Rα_{2} $, were detected only within allografts. The expression of IL-13 and IL-$ 13Rα_{2} $ resulted in significantly increased TGF-$ β_{1} $ levels (P <0.0001), higher numbers of $ CD11b^{high} %$ Gr1^{intermediate} $TGF-$ β_{1} $+ cells, and elevated cardiac collagen deposition (P = 0.0094). The allograft fibrosis found in these experiments was accompanied by upregulation of multiple profibrotic genes, which was confirmed by immunohistochemical stainings of allograft tissue. Blockage of the IL-13/TGF-$ β_{1} $ interaction by IL-$ 13Rα_{2} $ siRNA led to lower numbers of $ CD11b^{high} %$ Gr1^{intermediate} $TGF-$ β_{1} $+, $ CD4^{+} $, $ CD8^{+} $, and $ CD11b^{+} $ cells, and prevented collagen deposition (P = 0.0018) within these allografts. Conclusions IL-13 signaling via IL-$ 13Rα_{2} $ induces TGF-$ β_{1} $ and causes allograft fibrosis in a murine model of chronic transplant rejection. Blockage of this IL-13/TGF-$ β_{1} $ interaction by IL-$ 13Rα_{2} $ siRNA prevents cardiac allograft fibrosis. 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