Cathepsin S is the major activator of the psoriasis-associated proinflammatory cytokine IL-36[gamma]
The proinflammatory cytokine IL-36[gamma] is highly expressed in epithelial cells and is a pivotal mediator of epithelial inflammation. In particular, IL-36[gamma] is strongly associated with the inflammatory skin disease psoriasis. As with other IL-1 cytokines, IL-36[gamma] is expressed as an inact...
Ausführliche Beschreibung
Gespeichert in:
| Autor*in: |
Joseph S Ainscough [verfasserIn] |
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| Format: |
Artikel |
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| Sprache: |
Englisch |
| Erschienen: |
2017 |
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| Schlagwörter: |
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| Übergeordnetes Werk: |
Enthalten in: Proceedings of the National Academy of Sciences of the United States of America - Washington, DC : NAS, 1877, 114(2017), 13, Seite E2748 |
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| Übergeordnetes Werk: |
volume:114 ; year:2017 ; number:13 ; pages:E2748 |
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| 520 | |a The proinflammatory cytokine IL-36[gamma] is highly expressed in epithelial cells and is a pivotal mediator of epithelial inflammation. In particular, IL-36[gamma] is strongly associated with the inflammatory skin disease psoriasis. As with other IL-1 cytokines, IL-36[gamma] is expressed as an inactive precursor and must be processed by specific proteases to become bioactive. Our aim therefore was to identify protease/s capable of IL-36[gamma] activation and explore the importance of this activation in psoriasis. Using a keratinocyte-based activity assay in conjunction with small-molecule inhibitors and siRNA gene silencing, cathepsin S was identified as the major IL-36[gamma]-activating protease expressed by epithelial cells. Interestingly, cathepsin S activity was strongly up-regulated in samples extracted from psoriasis patients relative to healthy controls. In addition, IL-36[gamma]-Ser18, identified as the main product of cathepsin S-dependent IL-36[gamma] cleavage, induced psoriasiform changes in human skin-equivalent models. Together, these data provide important mechanistic insights into the activation of IL-36[gamma] and highlight that cathepsin S-mediated activation of IL-36[gamma] may be important in the development of numerous IL-36[gamma]-driven pathologies, in addition to psoriasis. | ||
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PQ20170501 (DE-627)OLC1993660011 (DE-599)GBVOLC1993660011 (PRQ)p577-d489d4e940005e97095d2a2e65603e4ad2ec49e6ac6c45121370161baebd15120 (KEY)0583363920170000114001302748cathepsinsisthemajoractivatorofthepsoriasisassocia DE-627 ger DE-627 rakwb eng 500 DE-101 570 AVZ LING fid BIODIV fid Joseph S Ainscough verfasserin aut Cathepsin S is the major activator of the psoriasis-associated proinflammatory cytokine IL-36[gamma] 2017 Text txt rdacontent ohne Hilfsmittel zu benutzen n rdamedia Band nc rdacarrier The proinflammatory cytokine IL-36[gamma] is highly expressed in epithelial cells and is a pivotal mediator of epithelial inflammation. In particular, IL-36[gamma] is strongly associated with the inflammatory skin disease psoriasis. As with other IL-1 cytokines, IL-36[gamma] is expressed as an inactive precursor and must be processed by specific proteases to become bioactive. Our aim therefore was to identify protease/s capable of IL-36[gamma] activation and explore the importance of this activation in psoriasis. Using a keratinocyte-based activity assay in conjunction with small-molecule inhibitors and siRNA gene silencing, cathepsin S was identified as the major IL-36[gamma]-activating protease expressed by epithelial cells. Interestingly, cathepsin S activity was strongly up-regulated in samples extracted from psoriasis patients relative to healthy controls. In addition, IL-36[gamma]-Ser18, identified as the main product of cathepsin S-dependent IL-36[gamma] cleavage, induced psoriasiform changes in human skin-equivalent models. Together, these data provide important mechanistic insights into the activation of IL-36[gamma] and highlight that cathepsin S-mediated activation of IL-36[gamma] may be important in the development of numerous IL-36[gamma]-driven pathologies, in addition to psoriasis. Cytokines Ribonucleic acid--RNA Proteases Cells Psoriasis Tom Macleod oth Dennis McGonagle oth Rosella Brakefield oth Jens M Baron oth Ade Alase oth Miriam Wittmann oth Martin Stacey oth Enthalten in Proceedings of the National Academy of Sciences of the United States of America Washington, DC : NAS, 1877 114(2017), 13, Seite E2748 (DE-627)129505269 (DE-600)209104-5 (DE-576)014909189 0027-8424 nnns volume:114 year:2017 number:13 pages:E2748 http://search.proquest.com/docview/1886313217 GBV_USEFLAG_A SYSFLAG_A GBV_OLC FID-LING FID-BIODIV SSG-OLC-PHY SSG-OLC-CHE SSG-OLC-MAT SSG-OLC-FOR SSG-OLC-PHA SSG-OLC-DE-84 SSG-OPC-MAT SSG-OPC-FOR GBV_ILN_40 GBV_ILN_59 AR 114 2017 13 E2748 |
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PQ20170501 (DE-627)OLC1993660011 (DE-599)GBVOLC1993660011 (PRQ)p577-d489d4e940005e97095d2a2e65603e4ad2ec49e6ac6c45121370161baebd15120 (KEY)0583363920170000114001302748cathepsinsisthemajoractivatorofthepsoriasisassocia DE-627 ger DE-627 rakwb eng 500 DE-101 570 AVZ LING fid BIODIV fid Joseph S Ainscough verfasserin aut Cathepsin S is the major activator of the psoriasis-associated proinflammatory cytokine IL-36[gamma] 2017 Text txt rdacontent ohne Hilfsmittel zu benutzen n rdamedia Band nc rdacarrier The proinflammatory cytokine IL-36[gamma] is highly expressed in epithelial cells and is a pivotal mediator of epithelial inflammation. In particular, IL-36[gamma] is strongly associated with the inflammatory skin disease psoriasis. As with other IL-1 cytokines, IL-36[gamma] is expressed as an inactive precursor and must be processed by specific proteases to become bioactive. Our aim therefore was to identify protease/s capable of IL-36[gamma] activation and explore the importance of this activation in psoriasis. Using a keratinocyte-based activity assay in conjunction with small-molecule inhibitors and siRNA gene silencing, cathepsin S was identified as the major IL-36[gamma]-activating protease expressed by epithelial cells. Interestingly, cathepsin S activity was strongly up-regulated in samples extracted from psoriasis patients relative to healthy controls. In addition, IL-36[gamma]-Ser18, identified as the main product of cathepsin S-dependent IL-36[gamma] cleavage, induced psoriasiform changes in human skin-equivalent models. Together, these data provide important mechanistic insights into the activation of IL-36[gamma] and highlight that cathepsin S-mediated activation of IL-36[gamma] may be important in the development of numerous IL-36[gamma]-driven pathologies, in addition to psoriasis. Cytokines Ribonucleic acid--RNA Proteases Cells Psoriasis Tom Macleod oth Dennis McGonagle oth Rosella Brakefield oth Jens M Baron oth Ade Alase oth Miriam Wittmann oth Martin Stacey oth Enthalten in Proceedings of the National Academy of Sciences of the United States of America Washington, DC : NAS, 1877 114(2017), 13, Seite E2748 (DE-627)129505269 (DE-600)209104-5 (DE-576)014909189 0027-8424 nnns volume:114 year:2017 number:13 pages:E2748 http://search.proquest.com/docview/1886313217 GBV_USEFLAG_A SYSFLAG_A GBV_OLC FID-LING FID-BIODIV SSG-OLC-PHY SSG-OLC-CHE SSG-OLC-MAT SSG-OLC-FOR SSG-OLC-PHA SSG-OLC-DE-84 SSG-OPC-MAT SSG-OPC-FOR GBV_ILN_40 GBV_ILN_59 AR 114 2017 13 E2748 |
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PQ20170501 (DE-627)OLC1993660011 (DE-599)GBVOLC1993660011 (PRQ)p577-d489d4e940005e97095d2a2e65603e4ad2ec49e6ac6c45121370161baebd15120 (KEY)0583363920170000114001302748cathepsinsisthemajoractivatorofthepsoriasisassocia DE-627 ger DE-627 rakwb eng 500 DE-101 570 AVZ LING fid BIODIV fid Joseph S Ainscough verfasserin aut Cathepsin S is the major activator of the psoriasis-associated proinflammatory cytokine IL-36[gamma] 2017 Text txt rdacontent ohne Hilfsmittel zu benutzen n rdamedia Band nc rdacarrier The proinflammatory cytokine IL-36[gamma] is highly expressed in epithelial cells and is a pivotal mediator of epithelial inflammation. In particular, IL-36[gamma] is strongly associated with the inflammatory skin disease psoriasis. As with other IL-1 cytokines, IL-36[gamma] is expressed as an inactive precursor and must be processed by specific proteases to become bioactive. Our aim therefore was to identify protease/s capable of IL-36[gamma] activation and explore the importance of this activation in psoriasis. Using a keratinocyte-based activity assay in conjunction with small-molecule inhibitors and siRNA gene silencing, cathepsin S was identified as the major IL-36[gamma]-activating protease expressed by epithelial cells. Interestingly, cathepsin S activity was strongly up-regulated in samples extracted from psoriasis patients relative to healthy controls. In addition, IL-36[gamma]-Ser18, identified as the main product of cathepsin S-dependent IL-36[gamma] cleavage, induced psoriasiform changes in human skin-equivalent models. Together, these data provide important mechanistic insights into the activation of IL-36[gamma] and highlight that cathepsin S-mediated activation of IL-36[gamma] may be important in the development of numerous IL-36[gamma]-driven pathologies, in addition to psoriasis. Cytokines Ribonucleic acid--RNA Proteases Cells Psoriasis Tom Macleod oth Dennis McGonagle oth Rosella Brakefield oth Jens M Baron oth Ade Alase oth Miriam Wittmann oth Martin Stacey oth Enthalten in Proceedings of the National Academy of Sciences of the United States of America Washington, DC : NAS, 1877 114(2017), 13, Seite E2748 (DE-627)129505269 (DE-600)209104-5 (DE-576)014909189 0027-8424 nnns volume:114 year:2017 number:13 pages:E2748 http://search.proquest.com/docview/1886313217 GBV_USEFLAG_A SYSFLAG_A GBV_OLC FID-LING FID-BIODIV SSG-OLC-PHY SSG-OLC-CHE SSG-OLC-MAT SSG-OLC-FOR SSG-OLC-PHA SSG-OLC-DE-84 SSG-OPC-MAT SSG-OPC-FOR GBV_ILN_40 GBV_ILN_59 AR 114 2017 13 E2748 |
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Enthalten in Proceedings of the National Academy of Sciences of the United States of America 114(2017), 13, Seite E2748 volume:114 year:2017 number:13 pages:E2748 |
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Joseph S Ainscough @@aut@@ Tom Macleod @@oth@@ Dennis McGonagle @@oth@@ Rosella Brakefield @@oth@@ Jens M Baron @@oth@@ Ade Alase @@oth@@ Miriam Wittmann @@oth@@ Martin Stacey @@oth@@ |
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cathepsin s is the major activator of the psoriasis-associated proinflammatory cytokine il-36[gamma] |
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Cathepsin S is the major activator of the psoriasis-associated proinflammatory cytokine IL-36[gamma] |
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The proinflammatory cytokine IL-36[gamma] is highly expressed in epithelial cells and is a pivotal mediator of epithelial inflammation. In particular, IL-36[gamma] is strongly associated with the inflammatory skin disease psoriasis. As with other IL-1 cytokines, IL-36[gamma] is expressed as an inactive precursor and must be processed by specific proteases to become bioactive. Our aim therefore was to identify protease/s capable of IL-36[gamma] activation and explore the importance of this activation in psoriasis. Using a keratinocyte-based activity assay in conjunction with small-molecule inhibitors and siRNA gene silencing, cathepsin S was identified as the major IL-36[gamma]-activating protease expressed by epithelial cells. Interestingly, cathepsin S activity was strongly up-regulated in samples extracted from psoriasis patients relative to healthy controls. In addition, IL-36[gamma]-Ser18, identified as the main product of cathepsin S-dependent IL-36[gamma] cleavage, induced psoriasiform changes in human skin-equivalent models. Together, these data provide important mechanistic insights into the activation of IL-36[gamma] and highlight that cathepsin S-mediated activation of IL-36[gamma] may be important in the development of numerous IL-36[gamma]-driven pathologies, in addition to psoriasis. |
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The proinflammatory cytokine IL-36[gamma] is highly expressed in epithelial cells and is a pivotal mediator of epithelial inflammation. In particular, IL-36[gamma] is strongly associated with the inflammatory skin disease psoriasis. As with other IL-1 cytokines, IL-36[gamma] is expressed as an inactive precursor and must be processed by specific proteases to become bioactive. Our aim therefore was to identify protease/s capable of IL-36[gamma] activation and explore the importance of this activation in psoriasis. Using a keratinocyte-based activity assay in conjunction with small-molecule inhibitors and siRNA gene silencing, cathepsin S was identified as the major IL-36[gamma]-activating protease expressed by epithelial cells. Interestingly, cathepsin S activity was strongly up-regulated in samples extracted from psoriasis patients relative to healthy controls. In addition, IL-36[gamma]-Ser18, identified as the main product of cathepsin S-dependent IL-36[gamma] cleavage, induced psoriasiform changes in human skin-equivalent models. Together, these data provide important mechanistic insights into the activation of IL-36[gamma] and highlight that cathepsin S-mediated activation of IL-36[gamma] may be important in the development of numerous IL-36[gamma]-driven pathologies, in addition to psoriasis. |
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The proinflammatory cytokine IL-36[gamma] is highly expressed in epithelial cells and is a pivotal mediator of epithelial inflammation. In particular, IL-36[gamma] is strongly associated with the inflammatory skin disease psoriasis. As with other IL-1 cytokines, IL-36[gamma] is expressed as an inactive precursor and must be processed by specific proteases to become bioactive. Our aim therefore was to identify protease/s capable of IL-36[gamma] activation and explore the importance of this activation in psoriasis. Using a keratinocyte-based activity assay in conjunction with small-molecule inhibitors and siRNA gene silencing, cathepsin S was identified as the major IL-36[gamma]-activating protease expressed by epithelial cells. Interestingly, cathepsin S activity was strongly up-regulated in samples extracted from psoriasis patients relative to healthy controls. In addition, IL-36[gamma]-Ser18, identified as the main product of cathepsin S-dependent IL-36[gamma] cleavage, induced psoriasiform changes in human skin-equivalent models. Together, these data provide important mechanistic insights into the activation of IL-36[gamma] and highlight that cathepsin S-mediated activation of IL-36[gamma] may be important in the development of numerous IL-36[gamma]-driven pathologies, in addition to psoriasis. |
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