Dexamethasone induces apoptosis in pulmonary arterial smooth muscle cells
Background Dexamethasone suppressed inflammation and haemodynamic changes in an animal model of pulmonary arterial hypertension (PAH). A major target for dexamethasone actions is NF-κB, which is activated in pulmonary vascular cells and perivascular inflammatory cells in PAH. Reverse remodelling is...
Ausführliche Beschreibung
Autor*in: |
Price, Laura C. [verfasserIn] |
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E-Artikel |
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Sprache: |
Englisch |
Erschienen: |
2015 |
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Schlagwörter: |
Pulmonary Arterial Hypertension Idiopathic Pulmonary Arterial Hypertension Pulmonary Artery Smooth Muscle Cell |
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Anmerkung: |
© Price et al. 2016 |
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Übergeordnetes Werk: |
Enthalten in: Respiratory research - London : BioMed Central, 2001, 16(2015), 1 vom: 18. Sept. |
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Übergeordnetes Werk: |
volume:16 ; year:2015 ; number:1 ; day:18 ; month:09 |
Links: |
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DOI / URN: |
10.1186/s12931-015-0262-y |
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Katalog-ID: |
SPR028519663 |
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520 | |a Background Dexamethasone suppressed inflammation and haemodynamic changes in an animal model of pulmonary arterial hypertension (PAH). A major target for dexamethasone actions is NF-κB, which is activated in pulmonary vascular cells and perivascular inflammatory cells in PAH. Reverse remodelling is an important concept in PAH disease therapy, and further to its anti-proliferative effects, we sought to explore whether dexamethasone augments pulmonary arterial smooth muscle cell (PASMC) apoptosis. Methods Analysis of apoptosis markers (caspase 3, in-situ DNA fragmentation) and NF-κB (p65 and phospho-IKK-α/β) activation was performed on lung tissue from rats with monocrotaline (MCT)-induced pulmonary hypertension (PH), before and after day 14–28 treatment with dexamethasone (5 mg/kg/day). PASMC were cultured from this rat PH model and from normal human lung following lung cancer surgery. Following stimulation with TNF-α (10 ng/ml), the effects of dexamethasone ($ 10^{−8} $–$ 10^{−6} $ M) and IKK2 (NF-κB) inhibition (AS602868, 0–3 μM (0-3×$ 10^{−6} $ M) on IL-6 and CXCL8 release and apoptosis was determined by ELISA and by Hoechst staining. NF-κB activation was measured by TransAm assay. Results Dexamethasone treatment of rats with MCT-induced PH in vivo led to PASMC apoptosis as displayed by increased caspase 3 expression and DNA fragmentation. A similar effect was seen in vitro using TNF-α-simulated human and rat PASMC following both dexamethasone and IKK2 inhibition. Increased apoptosis was associated with a reduction in NF-κB activation and in IL-6 and CXCL8 release from PASMC. Conclusions Dexamethasone exerted reverse-remodelling effects by augmenting apoptosis and reversing inflammation in PASMC possibly via inhibition of NF-κB. Future PAH therapies may involve targeting these important inflammatory pathways. | ||
650 | 4 | |a Pulmonary Arterial Hypertension |7 (dpeaa)DE-He213 | |
650 | 4 | |a Idiopathic Pulmonary Arterial Hypertension |7 (dpeaa)DE-He213 | |
650 | 4 | |a Pulmonary Artery Smooth Muscle Cell |7 (dpeaa)DE-He213 | |
650 | 4 | |a Pulmonary Arterial Smooth Muscle Cell |7 (dpeaa)DE-He213 | |
650 | 4 | |a Pulmonary Arterial Hypertension Therapy |7 (dpeaa)DE-He213 | |
700 | 1 | |a Shao, Dongmin |4 aut | |
700 | 1 | |a Meng, Chao |4 aut | |
700 | 1 | |a Perros, Frederic |4 aut | |
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700 | 1 | |a Zhu, Jie |4 aut | |
700 | 1 | |a Montani, David |4 aut | |
700 | 1 | |a Dorfmuller, Peter |4 aut | |
700 | 1 | |a Humbert, Marc |4 aut | |
700 | 1 | |a Adcock, Ian M. |4 aut | |
700 | 1 | |a Wort, Stephen J. |4 aut | |
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10.1186/s12931-015-0262-y doi (DE-627)SPR028519663 (SPR)s12931-015-0262-y-e DE-627 ger DE-627 rakwb eng Price, Laura C. verfasserin aut Dexamethasone induces apoptosis in pulmonary arterial smooth muscle cells 2015 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © Price et al. 2016 Background Dexamethasone suppressed inflammation and haemodynamic changes in an animal model of pulmonary arterial hypertension (PAH). A major target for dexamethasone actions is NF-κB, which is activated in pulmonary vascular cells and perivascular inflammatory cells in PAH. Reverse remodelling is an important concept in PAH disease therapy, and further to its anti-proliferative effects, we sought to explore whether dexamethasone augments pulmonary arterial smooth muscle cell (PASMC) apoptosis. Methods Analysis of apoptosis markers (caspase 3, in-situ DNA fragmentation) and NF-κB (p65 and phospho-IKK-α/β) activation was performed on lung tissue from rats with monocrotaline (MCT)-induced pulmonary hypertension (PH), before and after day 14–28 treatment with dexamethasone (5 mg/kg/day). PASMC were cultured from this rat PH model and from normal human lung following lung cancer surgery. Following stimulation with TNF-α (10 ng/ml), the effects of dexamethasone ($ 10^{−8} $–$ 10^{−6} $ M) and IKK2 (NF-κB) inhibition (AS602868, 0–3 μM (0-3×$ 10^{−6} $ M) on IL-6 and CXCL8 release and apoptosis was determined by ELISA and by Hoechst staining. NF-κB activation was measured by TransAm assay. Results Dexamethasone treatment of rats with MCT-induced PH in vivo led to PASMC apoptosis as displayed by increased caspase 3 expression and DNA fragmentation. A similar effect was seen in vitro using TNF-α-simulated human and rat PASMC following both dexamethasone and IKK2 inhibition. Increased apoptosis was associated with a reduction in NF-κB activation and in IL-6 and CXCL8 release from PASMC. Conclusions Dexamethasone exerted reverse-remodelling effects by augmenting apoptosis and reversing inflammation in PASMC possibly via inhibition of NF-κB. Future PAH therapies may involve targeting these important inflammatory pathways. Pulmonary Arterial Hypertension (dpeaa)DE-He213 Idiopathic Pulmonary Arterial Hypertension (dpeaa)DE-He213 Pulmonary Artery Smooth Muscle Cell (dpeaa)DE-He213 Pulmonary Arterial Smooth Muscle Cell (dpeaa)DE-He213 Pulmonary Arterial Hypertension Therapy (dpeaa)DE-He213 Shao, Dongmin aut Meng, Chao aut Perros, Frederic aut Garfield, Benjamin E. aut Zhu, Jie aut Montani, David aut Dorfmuller, Peter aut Humbert, Marc aut Adcock, Ian M. aut Wort, Stephen J. aut Enthalten in Respiratory research London : BioMed Central, 2001 16(2015), 1 vom: 18. Sept. (DE-627)326646485 (DE-600)2041675-1 1465-993X nnns volume:16 year:2015 number:1 day:18 month:09 https://dx.doi.org/10.1186/s12931-015-0262-y kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 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_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2031 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2057 GBV_ILN_2061 GBV_ILN_2111 GBV_ILN_2113 GBV_ILN_2153 GBV_ILN_2190 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 16 2015 1 18 09 |
spelling |
10.1186/s12931-015-0262-y doi (DE-627)SPR028519663 (SPR)s12931-015-0262-y-e DE-627 ger DE-627 rakwb eng Price, Laura C. verfasserin aut Dexamethasone induces apoptosis in pulmonary arterial smooth muscle cells 2015 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © Price et al. 2016 Background Dexamethasone suppressed inflammation and haemodynamic changes in an animal model of pulmonary arterial hypertension (PAH). A major target for dexamethasone actions is NF-κB, which is activated in pulmonary vascular cells and perivascular inflammatory cells in PAH. Reverse remodelling is an important concept in PAH disease therapy, and further to its anti-proliferative effects, we sought to explore whether dexamethasone augments pulmonary arterial smooth muscle cell (PASMC) apoptosis. Methods Analysis of apoptosis markers (caspase 3, in-situ DNA fragmentation) and NF-κB (p65 and phospho-IKK-α/β) activation was performed on lung tissue from rats with monocrotaline (MCT)-induced pulmonary hypertension (PH), before and after day 14–28 treatment with dexamethasone (5 mg/kg/day). PASMC were cultured from this rat PH model and from normal human lung following lung cancer surgery. Following stimulation with TNF-α (10 ng/ml), the effects of dexamethasone ($ 10^{−8} $–$ 10^{−6} $ M) and IKK2 (NF-κB) inhibition (AS602868, 0–3 μM (0-3×$ 10^{−6} $ M) on IL-6 and CXCL8 release and apoptosis was determined by ELISA and by Hoechst staining. NF-κB activation was measured by TransAm assay. Results Dexamethasone treatment of rats with MCT-induced PH in vivo led to PASMC apoptosis as displayed by increased caspase 3 expression and DNA fragmentation. A similar effect was seen in vitro using TNF-α-simulated human and rat PASMC following both dexamethasone and IKK2 inhibition. Increased apoptosis was associated with a reduction in NF-κB activation and in IL-6 and CXCL8 release from PASMC. Conclusions Dexamethasone exerted reverse-remodelling effects by augmenting apoptosis and reversing inflammation in PASMC possibly via inhibition of NF-κB. Future PAH therapies may involve targeting these important inflammatory pathways. Pulmonary Arterial Hypertension (dpeaa)DE-He213 Idiopathic Pulmonary Arterial Hypertension (dpeaa)DE-He213 Pulmonary Artery Smooth Muscle Cell (dpeaa)DE-He213 Pulmonary Arterial Smooth Muscle Cell (dpeaa)DE-He213 Pulmonary Arterial Hypertension Therapy (dpeaa)DE-He213 Shao, Dongmin aut Meng, Chao aut Perros, Frederic aut Garfield, Benjamin E. aut Zhu, Jie aut Montani, David aut Dorfmuller, Peter aut Humbert, Marc aut Adcock, Ian M. aut Wort, Stephen J. aut Enthalten in Respiratory research London : BioMed Central, 2001 16(2015), 1 vom: 18. Sept. (DE-627)326646485 (DE-600)2041675-1 1465-993X nnns volume:16 year:2015 number:1 day:18 month:09 https://dx.doi.org/10.1186/s12931-015-0262-y kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 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_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2031 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2057 GBV_ILN_2061 GBV_ILN_2111 GBV_ILN_2113 GBV_ILN_2153 GBV_ILN_2190 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 16 2015 1 18 09 |
allfields_unstemmed |
10.1186/s12931-015-0262-y doi (DE-627)SPR028519663 (SPR)s12931-015-0262-y-e DE-627 ger DE-627 rakwb eng Price, Laura C. verfasserin aut Dexamethasone induces apoptosis in pulmonary arterial smooth muscle cells 2015 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © Price et al. 2016 Background Dexamethasone suppressed inflammation and haemodynamic changes in an animal model of pulmonary arterial hypertension (PAH). A major target for dexamethasone actions is NF-κB, which is activated in pulmonary vascular cells and perivascular inflammatory cells in PAH. Reverse remodelling is an important concept in PAH disease therapy, and further to its anti-proliferative effects, we sought to explore whether dexamethasone augments pulmonary arterial smooth muscle cell (PASMC) apoptosis. Methods Analysis of apoptosis markers (caspase 3, in-situ DNA fragmentation) and NF-κB (p65 and phospho-IKK-α/β) activation was performed on lung tissue from rats with monocrotaline (MCT)-induced pulmonary hypertension (PH), before and after day 14–28 treatment with dexamethasone (5 mg/kg/day). PASMC were cultured from this rat PH model and from normal human lung following lung cancer surgery. Following stimulation with TNF-α (10 ng/ml), the effects of dexamethasone ($ 10^{−8} $–$ 10^{−6} $ M) and IKK2 (NF-κB) inhibition (AS602868, 0–3 μM (0-3×$ 10^{−6} $ M) on IL-6 and CXCL8 release and apoptosis was determined by ELISA and by Hoechst staining. NF-κB activation was measured by TransAm assay. Results Dexamethasone treatment of rats with MCT-induced PH in vivo led to PASMC apoptosis as displayed by increased caspase 3 expression and DNA fragmentation. A similar effect was seen in vitro using TNF-α-simulated human and rat PASMC following both dexamethasone and IKK2 inhibition. Increased apoptosis was associated with a reduction in NF-κB activation and in IL-6 and CXCL8 release from PASMC. Conclusions Dexamethasone exerted reverse-remodelling effects by augmenting apoptosis and reversing inflammation in PASMC possibly via inhibition of NF-κB. Future PAH therapies may involve targeting these important inflammatory pathways. Pulmonary Arterial Hypertension (dpeaa)DE-He213 Idiopathic Pulmonary Arterial Hypertension (dpeaa)DE-He213 Pulmonary Artery Smooth Muscle Cell (dpeaa)DE-He213 Pulmonary Arterial Smooth Muscle Cell (dpeaa)DE-He213 Pulmonary Arterial Hypertension Therapy (dpeaa)DE-He213 Shao, Dongmin aut Meng, Chao aut Perros, Frederic aut Garfield, Benjamin E. aut Zhu, Jie aut Montani, David aut Dorfmuller, Peter aut Humbert, Marc aut Adcock, Ian M. aut Wort, Stephen J. aut Enthalten in Respiratory research London : BioMed Central, 2001 16(2015), 1 vom: 18. Sept. (DE-627)326646485 (DE-600)2041675-1 1465-993X nnns volume:16 year:2015 number:1 day:18 month:09 https://dx.doi.org/10.1186/s12931-015-0262-y kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 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_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2031 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2057 GBV_ILN_2061 GBV_ILN_2111 GBV_ILN_2113 GBV_ILN_2153 GBV_ILN_2190 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 16 2015 1 18 09 |
allfieldsGer |
10.1186/s12931-015-0262-y doi (DE-627)SPR028519663 (SPR)s12931-015-0262-y-e DE-627 ger DE-627 rakwb eng Price, Laura C. verfasserin aut Dexamethasone induces apoptosis in pulmonary arterial smooth muscle cells 2015 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © Price et al. 2016 Background Dexamethasone suppressed inflammation and haemodynamic changes in an animal model of pulmonary arterial hypertension (PAH). A major target for dexamethasone actions is NF-κB, which is activated in pulmonary vascular cells and perivascular inflammatory cells in PAH. Reverse remodelling is an important concept in PAH disease therapy, and further to its anti-proliferative effects, we sought to explore whether dexamethasone augments pulmonary arterial smooth muscle cell (PASMC) apoptosis. Methods Analysis of apoptosis markers (caspase 3, in-situ DNA fragmentation) and NF-κB (p65 and phospho-IKK-α/β) activation was performed on lung tissue from rats with monocrotaline (MCT)-induced pulmonary hypertension (PH), before and after day 14–28 treatment with dexamethasone (5 mg/kg/day). PASMC were cultured from this rat PH model and from normal human lung following lung cancer surgery. Following stimulation with TNF-α (10 ng/ml), the effects of dexamethasone ($ 10^{−8} $–$ 10^{−6} $ M) and IKK2 (NF-κB) inhibition (AS602868, 0–3 μM (0-3×$ 10^{−6} $ M) on IL-6 and CXCL8 release and apoptosis was determined by ELISA and by Hoechst staining. NF-κB activation was measured by TransAm assay. Results Dexamethasone treatment of rats with MCT-induced PH in vivo led to PASMC apoptosis as displayed by increased caspase 3 expression and DNA fragmentation. A similar effect was seen in vitro using TNF-α-simulated human and rat PASMC following both dexamethasone and IKK2 inhibition. Increased apoptosis was associated with a reduction in NF-κB activation and in IL-6 and CXCL8 release from PASMC. Conclusions Dexamethasone exerted reverse-remodelling effects by augmenting apoptosis and reversing inflammation in PASMC possibly via inhibition of NF-κB. Future PAH therapies may involve targeting these important inflammatory pathways. Pulmonary Arterial Hypertension (dpeaa)DE-He213 Idiopathic Pulmonary Arterial Hypertension (dpeaa)DE-He213 Pulmonary Artery Smooth Muscle Cell (dpeaa)DE-He213 Pulmonary Arterial Smooth Muscle Cell (dpeaa)DE-He213 Pulmonary Arterial Hypertension Therapy (dpeaa)DE-He213 Shao, Dongmin aut Meng, Chao aut Perros, Frederic aut Garfield, Benjamin E. aut Zhu, Jie aut Montani, David aut Dorfmuller, Peter aut Humbert, Marc aut Adcock, Ian M. aut Wort, Stephen J. aut Enthalten in Respiratory research London : BioMed Central, 2001 16(2015), 1 vom: 18. Sept. (DE-627)326646485 (DE-600)2041675-1 1465-993X nnns volume:16 year:2015 number:1 day:18 month:09 https://dx.doi.org/10.1186/s12931-015-0262-y kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 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_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2031 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2057 GBV_ILN_2061 GBV_ILN_2111 GBV_ILN_2113 GBV_ILN_2153 GBV_ILN_2190 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 16 2015 1 18 09 |
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10.1186/s12931-015-0262-y doi (DE-627)SPR028519663 (SPR)s12931-015-0262-y-e DE-627 ger DE-627 rakwb eng Price, Laura C. verfasserin aut Dexamethasone induces apoptosis in pulmonary arterial smooth muscle cells 2015 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © Price et al. 2016 Background Dexamethasone suppressed inflammation and haemodynamic changes in an animal model of pulmonary arterial hypertension (PAH). A major target for dexamethasone actions is NF-κB, which is activated in pulmonary vascular cells and perivascular inflammatory cells in PAH. Reverse remodelling is an important concept in PAH disease therapy, and further to its anti-proliferative effects, we sought to explore whether dexamethasone augments pulmonary arterial smooth muscle cell (PASMC) apoptosis. Methods Analysis of apoptosis markers (caspase 3, in-situ DNA fragmentation) and NF-κB (p65 and phospho-IKK-α/β) activation was performed on lung tissue from rats with monocrotaline (MCT)-induced pulmonary hypertension (PH), before and after day 14–28 treatment with dexamethasone (5 mg/kg/day). PASMC were cultured from this rat PH model and from normal human lung following lung cancer surgery. Following stimulation with TNF-α (10 ng/ml), the effects of dexamethasone ($ 10^{−8} $–$ 10^{−6} $ M) and IKK2 (NF-κB) inhibition (AS602868, 0–3 μM (0-3×$ 10^{−6} $ M) on IL-6 and CXCL8 release and apoptosis was determined by ELISA and by Hoechst staining. NF-κB activation was measured by TransAm assay. Results Dexamethasone treatment of rats with MCT-induced PH in vivo led to PASMC apoptosis as displayed by increased caspase 3 expression and DNA fragmentation. A similar effect was seen in vitro using TNF-α-simulated human and rat PASMC following both dexamethasone and IKK2 inhibition. Increased apoptosis was associated with a reduction in NF-κB activation and in IL-6 and CXCL8 release from PASMC. Conclusions Dexamethasone exerted reverse-remodelling effects by augmenting apoptosis and reversing inflammation in PASMC possibly via inhibition of NF-κB. Future PAH therapies may involve targeting these important inflammatory pathways. Pulmonary Arterial Hypertension (dpeaa)DE-He213 Idiopathic Pulmonary Arterial Hypertension (dpeaa)DE-He213 Pulmonary Artery Smooth Muscle Cell (dpeaa)DE-He213 Pulmonary Arterial Smooth Muscle Cell (dpeaa)DE-He213 Pulmonary Arterial Hypertension Therapy (dpeaa)DE-He213 Shao, Dongmin aut Meng, Chao aut Perros, Frederic aut Garfield, Benjamin E. aut Zhu, Jie aut Montani, David aut Dorfmuller, Peter aut Humbert, Marc aut Adcock, Ian M. aut Wort, Stephen J. aut Enthalten in Respiratory research London : BioMed Central, 2001 16(2015), 1 vom: 18. Sept. (DE-627)326646485 (DE-600)2041675-1 1465-993X nnns volume:16 year:2015 number:1 day:18 month:09 https://dx.doi.org/10.1186/s12931-015-0262-y kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 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_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2031 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2057 GBV_ILN_2061 GBV_ILN_2111 GBV_ILN_2113 GBV_ILN_2153 GBV_ILN_2190 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 16 2015 1 18 09 |
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Dexamethasone induces apoptosis in pulmonary arterial smooth muscle cells Pulmonary Arterial Hypertension (dpeaa)DE-He213 Idiopathic Pulmonary Arterial Hypertension (dpeaa)DE-He213 Pulmonary Artery Smooth Muscle Cell (dpeaa)DE-He213 Pulmonary Arterial Smooth Muscle Cell (dpeaa)DE-He213 Pulmonary Arterial Hypertension Therapy (dpeaa)DE-He213 |
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Dexamethasone induces apoptosis in pulmonary arterial smooth muscle cells |
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Dexamethasone induces apoptosis in pulmonary arterial smooth muscle cells |
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Price, Laura C. |
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Price, Laura C. Shao, Dongmin Meng, Chao Perros, Frederic Garfield, Benjamin E. Zhu, Jie Montani, David Dorfmuller, Peter Humbert, Marc Adcock, Ian M. Wort, Stephen J. |
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dexamethasone induces apoptosis in pulmonary arterial smooth muscle cells |
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Dexamethasone induces apoptosis in pulmonary arterial smooth muscle cells |
abstract |
Background Dexamethasone suppressed inflammation and haemodynamic changes in an animal model of pulmonary arterial hypertension (PAH). A major target for dexamethasone actions is NF-κB, which is activated in pulmonary vascular cells and perivascular inflammatory cells in PAH. Reverse remodelling is an important concept in PAH disease therapy, and further to its anti-proliferative effects, we sought to explore whether dexamethasone augments pulmonary arterial smooth muscle cell (PASMC) apoptosis. Methods Analysis of apoptosis markers (caspase 3, in-situ DNA fragmentation) and NF-κB (p65 and phospho-IKK-α/β) activation was performed on lung tissue from rats with monocrotaline (MCT)-induced pulmonary hypertension (PH), before and after day 14–28 treatment with dexamethasone (5 mg/kg/day). PASMC were cultured from this rat PH model and from normal human lung following lung cancer surgery. Following stimulation with TNF-α (10 ng/ml), the effects of dexamethasone ($ 10^{−8} $–$ 10^{−6} $ M) and IKK2 (NF-κB) inhibition (AS602868, 0–3 μM (0-3×$ 10^{−6} $ M) on IL-6 and CXCL8 release and apoptosis was determined by ELISA and by Hoechst staining. NF-κB activation was measured by TransAm assay. Results Dexamethasone treatment of rats with MCT-induced PH in vivo led to PASMC apoptosis as displayed by increased caspase 3 expression and DNA fragmentation. A similar effect was seen in vitro using TNF-α-simulated human and rat PASMC following both dexamethasone and IKK2 inhibition. Increased apoptosis was associated with a reduction in NF-κB activation and in IL-6 and CXCL8 release from PASMC. Conclusions Dexamethasone exerted reverse-remodelling effects by augmenting apoptosis and reversing inflammation in PASMC possibly via inhibition of NF-κB. Future PAH therapies may involve targeting these important inflammatory pathways. © Price et al. 2016 |
abstractGer |
Background Dexamethasone suppressed inflammation and haemodynamic changes in an animal model of pulmonary arterial hypertension (PAH). A major target for dexamethasone actions is NF-κB, which is activated in pulmonary vascular cells and perivascular inflammatory cells in PAH. Reverse remodelling is an important concept in PAH disease therapy, and further to its anti-proliferative effects, we sought to explore whether dexamethasone augments pulmonary arterial smooth muscle cell (PASMC) apoptosis. Methods Analysis of apoptosis markers (caspase 3, in-situ DNA fragmentation) and NF-κB (p65 and phospho-IKK-α/β) activation was performed on lung tissue from rats with monocrotaline (MCT)-induced pulmonary hypertension (PH), before and after day 14–28 treatment with dexamethasone (5 mg/kg/day). PASMC were cultured from this rat PH model and from normal human lung following lung cancer surgery. Following stimulation with TNF-α (10 ng/ml), the effects of dexamethasone ($ 10^{−8} $–$ 10^{−6} $ M) and IKK2 (NF-κB) inhibition (AS602868, 0–3 μM (0-3×$ 10^{−6} $ M) on IL-6 and CXCL8 release and apoptosis was determined by ELISA and by Hoechst staining. NF-κB activation was measured by TransAm assay. Results Dexamethasone treatment of rats with MCT-induced PH in vivo led to PASMC apoptosis as displayed by increased caspase 3 expression and DNA fragmentation. A similar effect was seen in vitro using TNF-α-simulated human and rat PASMC following both dexamethasone and IKK2 inhibition. Increased apoptosis was associated with a reduction in NF-κB activation and in IL-6 and CXCL8 release from PASMC. Conclusions Dexamethasone exerted reverse-remodelling effects by augmenting apoptosis and reversing inflammation in PASMC possibly via inhibition of NF-κB. Future PAH therapies may involve targeting these important inflammatory pathways. © Price et al. 2016 |
abstract_unstemmed |
Background Dexamethasone suppressed inflammation and haemodynamic changes in an animal model of pulmonary arterial hypertension (PAH). A major target for dexamethasone actions is NF-κB, which is activated in pulmonary vascular cells and perivascular inflammatory cells in PAH. Reverse remodelling is an important concept in PAH disease therapy, and further to its anti-proliferative effects, we sought to explore whether dexamethasone augments pulmonary arterial smooth muscle cell (PASMC) apoptosis. Methods Analysis of apoptosis markers (caspase 3, in-situ DNA fragmentation) and NF-κB (p65 and phospho-IKK-α/β) activation was performed on lung tissue from rats with monocrotaline (MCT)-induced pulmonary hypertension (PH), before and after day 14–28 treatment with dexamethasone (5 mg/kg/day). PASMC were cultured from this rat PH model and from normal human lung following lung cancer surgery. Following stimulation with TNF-α (10 ng/ml), the effects of dexamethasone ($ 10^{−8} $–$ 10^{−6} $ M) and IKK2 (NF-κB) inhibition (AS602868, 0–3 μM (0-3×$ 10^{−6} $ M) on IL-6 and CXCL8 release and apoptosis was determined by ELISA and by Hoechst staining. NF-κB activation was measured by TransAm assay. Results Dexamethasone treatment of rats with MCT-induced PH in vivo led to PASMC apoptosis as displayed by increased caspase 3 expression and DNA fragmentation. A similar effect was seen in vitro using TNF-α-simulated human and rat PASMC following both dexamethasone and IKK2 inhibition. Increased apoptosis was associated with a reduction in NF-κB activation and in IL-6 and CXCL8 release from PASMC. Conclusions Dexamethasone exerted reverse-remodelling effects by augmenting apoptosis and reversing inflammation in PASMC possibly via inhibition of NF-κB. Future PAH therapies may involve targeting these important inflammatory pathways. © Price et al. 2016 |
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