Abstract
Highlights: • Nuclear IL-33 expression is reduced in vascular endothelial cells from PAH patients. • Knockdown of IL-33 leads to increased IL-6 and sST2 mRNA expression. • IL-33 binds homeobox motifs in target gene promoters and recruits repressor proteins. - Abstract: Idiopathic pulmonary arterial hypertension (IPAH) is an incurable condition leading to right ventricular failure and death and inflammation is postulated to be associated with vascular remodelling. Interleukin (IL)-33, a member of the “alarmin” family can either act on the membrane ST2 receptor or as a nuclear repressor, to regulate inflammation. We show, using immunohistochemistry, that IL-33 expression is nuclear in the vessels of healthy subjects whereas nuclear IL-33 is markedly diminished in the vessels of IPAH patients. This correlates with reduced IL-33 mRNA expression in their lung. In contrast, serum levels of IL-33 are unchanged in IPAH. However, the expression of the soluble form of ST2, sST2, is enhanced in the serum of IPAH patients. Knock-down of IL-33 in human endothelial cells (ECs) using siRNA is associated with selective modulation of inflammatory genes involved in vascular remodelling including IL-6. Additionally, IL-33 knock-down significantly increased sST2 release from ECs. Chromatin immunoprecipitation demonstrated that IL-33 bound multiple putative homeodomain protein binding
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Shao, Dongmin;
[1]
Perros, Frédéric;
[2]
Caramori, Gaetano;
[3]
Meng, Chao;
[1]
Department of Geriatrics, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai (China)];
Dormuller, Peter;
[2]
Chou, Pai-Chien;
[4]
Church, Colin;
[5]
Papi, Alberto;
Casolari, Paolo;
[3]
Welsh, David;
Peacock, Andrew;
[5]
Humbert, Marc;
[2]
Adcock, Ian M.;
[4]
Wort, Stephen J., E-mail: s.wort@imperial.ac.uk
[1]
- Section of Vascular Biology, National Heart and Lung Institute, Imperial College London, London (United Kingdom)
- Faculté de Médecine, Université Paris-Sud, Paris, Clamart (France)
- Dipartimento di Scienze Mediche, Sezione di Medicina Interna e Cardiorespiratoria, Centro Interdipartimentale per lo Studio delle Malattie Infiammatorie delle Vie Aeree e Patologie Fumo-Correlate, University of Ferrara, Ferrara (Italy)
- Airways Disease, National Heart and Lung Institute (United Kingdom)
- Scottish Pulmonary Vascular Unit, University of Glasgow (United Kingdom)
Citation Formats
Shao, Dongmin, Perros, Frédéric, Caramori, Gaetano, Meng, Chao, Department of Geriatrics, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai (China)], Dormuller, Peter, Chou, Pai-Chien, Church, Colin, Papi, Alberto, Casolari, Paolo, Welsh, David, Peacock, Andrew, Humbert, Marc, Adcock, Ian M., and Wort, Stephen J., E-mail: s.wort@imperial.ac.uk.
Nuclear IL-33 regulates soluble ST2 receptor and IL-6 expression in primary human arterial endothelial cells and is decreased in idiopathic pulmonary arterial hypertension.
United States: N. p.,
2014.
Web.
doi:10.1016/J.BBRC.2014.06.111.
Shao, Dongmin, Perros, Frédéric, Caramori, Gaetano, Meng, Chao, Department of Geriatrics, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai (China)], Dormuller, Peter, Chou, Pai-Chien, Church, Colin, Papi, Alberto, Casolari, Paolo, Welsh, David, Peacock, Andrew, Humbert, Marc, Adcock, Ian M., & Wort, Stephen J., E-mail: s.wort@imperial.ac.uk.
Nuclear IL-33 regulates soluble ST2 receptor and IL-6 expression in primary human arterial endothelial cells and is decreased in idiopathic pulmonary arterial hypertension.
United States.
https://doi.org/10.1016/J.BBRC.2014.06.111
Shao, Dongmin, Perros, Frédéric, Caramori, Gaetano, Meng, Chao, Department of Geriatrics, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai (China)], Dormuller, Peter, Chou, Pai-Chien, Church, Colin, Papi, Alberto, Casolari, Paolo, Welsh, David, Peacock, Andrew, Humbert, Marc, Adcock, Ian M., and Wort, Stephen J., E-mail: s.wort@imperial.ac.uk.
2014.
"Nuclear IL-33 regulates soluble ST2 receptor and IL-6 expression in primary human arterial endothelial cells and is decreased in idiopathic pulmonary arterial hypertension."
United States.
https://doi.org/10.1016/J.BBRC.2014.06.111.
@misc{etde_22416707,
title = {Nuclear IL-33 regulates soluble ST2 receptor and IL-6 expression in primary human arterial endothelial cells and is decreased in idiopathic pulmonary arterial hypertension}
author = {Shao, Dongmin, Perros, Frédéric, Caramori, Gaetano, Meng, Chao, Department of Geriatrics, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai (China)], Dormuller, Peter, Chou, Pai-Chien, Church, Colin, Papi, Alberto, Casolari, Paolo, Welsh, David, Peacock, Andrew, Humbert, Marc, Adcock, Ian M., and Wort, Stephen J., E-mail: s.wort@imperial.ac.uk}
abstractNote = {Highlights: • Nuclear IL-33 expression is reduced in vascular endothelial cells from PAH patients. • Knockdown of IL-33 leads to increased IL-6 and sST2 mRNA expression. • IL-33 binds homeobox motifs in target gene promoters and recruits repressor proteins. - Abstract: Idiopathic pulmonary arterial hypertension (IPAH) is an incurable condition leading to right ventricular failure and death and inflammation is postulated to be associated with vascular remodelling. Interleukin (IL)-33, a member of the “alarmin” family can either act on the membrane ST2 receptor or as a nuclear repressor, to regulate inflammation. We show, using immunohistochemistry, that IL-33 expression is nuclear in the vessels of healthy subjects whereas nuclear IL-33 is markedly diminished in the vessels of IPAH patients. This correlates with reduced IL-33 mRNA expression in their lung. In contrast, serum levels of IL-33 are unchanged in IPAH. However, the expression of the soluble form of ST2, sST2, is enhanced in the serum of IPAH patients. Knock-down of IL-33 in human endothelial cells (ECs) using siRNA is associated with selective modulation of inflammatory genes involved in vascular remodelling including IL-6. Additionally, IL-33 knock-down significantly increased sST2 release from ECs. Chromatin immunoprecipitation demonstrated that IL-33 bound multiple putative homeodomain protein binding motifs in the proximal and distal promoters of ST2 genes. IL-33 formed a complex with the histone methyltransferase SUV39H1, a transcriptional repressor. In conclusion, IL-33 regulates the expression of IL-6 and sST2, an endogenous IL-33 inhibitor, in primary human ECs and may play an important role in the pathogenesis of PAH through recruitment of transcriptional repressor proteins.}
doi = {10.1016/J.BBRC.2014.06.111}
journal = []
issue = {1}
volume = {451}
journal type = {AC}
place = {United States}
year = {2014}
month = {Aug}
}
title = {Nuclear IL-33 regulates soluble ST2 receptor and IL-6 expression in primary human arterial endothelial cells and is decreased in idiopathic pulmonary arterial hypertension}
author = {Shao, Dongmin, Perros, Frédéric, Caramori, Gaetano, Meng, Chao, Department of Geriatrics, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai (China)], Dormuller, Peter, Chou, Pai-Chien, Church, Colin, Papi, Alberto, Casolari, Paolo, Welsh, David, Peacock, Andrew, Humbert, Marc, Adcock, Ian M., and Wort, Stephen J., E-mail: s.wort@imperial.ac.uk}
abstractNote = {Highlights: • Nuclear IL-33 expression is reduced in vascular endothelial cells from PAH patients. • Knockdown of IL-33 leads to increased IL-6 and sST2 mRNA expression. • IL-33 binds homeobox motifs in target gene promoters and recruits repressor proteins. - Abstract: Idiopathic pulmonary arterial hypertension (IPAH) is an incurable condition leading to right ventricular failure and death and inflammation is postulated to be associated with vascular remodelling. Interleukin (IL)-33, a member of the “alarmin” family can either act on the membrane ST2 receptor or as a nuclear repressor, to regulate inflammation. We show, using immunohistochemistry, that IL-33 expression is nuclear in the vessels of healthy subjects whereas nuclear IL-33 is markedly diminished in the vessels of IPAH patients. This correlates with reduced IL-33 mRNA expression in their lung. In contrast, serum levels of IL-33 are unchanged in IPAH. However, the expression of the soluble form of ST2, sST2, is enhanced in the serum of IPAH patients. Knock-down of IL-33 in human endothelial cells (ECs) using siRNA is associated with selective modulation of inflammatory genes involved in vascular remodelling including IL-6. Additionally, IL-33 knock-down significantly increased sST2 release from ECs. Chromatin immunoprecipitation demonstrated that IL-33 bound multiple putative homeodomain protein binding motifs in the proximal and distal promoters of ST2 genes. IL-33 formed a complex with the histone methyltransferase SUV39H1, a transcriptional repressor. In conclusion, IL-33 regulates the expression of IL-6 and sST2, an endogenous IL-33 inhibitor, in primary human ECs and may play an important role in the pathogenesis of PAH through recruitment of transcriptional repressor proteins.}
doi = {10.1016/J.BBRC.2014.06.111}
journal = []
issue = {1}
volume = {451}
journal type = {AC}
place = {United States}
year = {2014}
month = {Aug}
}