Abstract:
BACKGROUND:Bronchial fibroblasts are the main structural cells responsible for extracellular matrix production and turnover in lung tissue. They play a key role in airway remodelling in asthma through different cytokines including interleukin (IL-6). OBJECTIVE:To decipher IL-6 signalling in bronchial fibroblasts obtained from severe eosinophilic asthmatics compared to mild asthmatics and healthy controls. METHODS:Human bronchial fibroblasts were isolated from bronchial biopsies of mild and severe eosinophilic asthmatics and non-atopic healthy controls. IL-6 was assessed by qRT-PCR and ELISA. Phosphorylated STAT3, SHP2 and p38/MAPK were evaluated by Western blot. Chemical inhibitors for SHP2 and p38 were used. Fibroblast proliferation was evaluated by BrdU incorporation test. RESULTS:IL-6 release was significantly increased in fibroblasts from mild and severe asthmatics compared to healthy controls. Fibroblasts from severe asthmatics showed a reduced STAT3 activation compared to mild asthmatics and healthy controls. Constitutive activation of phosphatase SHP2 was found to negatively regulate IL-6 induced STAT3 phosphorylation in fibroblasts from severe asthmatics. This effect was accompanied by a decrease in fibroblast proliferation rate due to the activated p38/mitogen-activated protein kinase. SHP2 and p38/MAPK specific inhibitors (PHPS1 and SB212190) significantly induce a restoration of STAT3 phosphorylation, IL-6 target gene expression and cell proliferation. CONCLUSION:These data show dysregulated IL-6 signalling in bronchial fibroblasts derived from severe eosinophilic asthmatic subjects involving the protein tyrosine phosphatase SHP2 and p38MAPK. Collectively, our data provides new insights into the mechanisms by which bronchial fibroblasts regulate airway remodelling in severe asthma.
journal_name
Cell Signaljournal_title
Cellular signallingauthors
Salem IH,Plante S,Gounni AS,Rouabhia M,Chakir Jdoi
10.1016/j.cellsig.2017.12.001subject
Has Abstractpub_date
2018-03-01 00:00:00pages
47-54eissn
0898-6568issn
1873-3913pii
S0898-6568(17)30321-2journal_volume
43pub_type
杂志文章abstract::Pseudoxanthoma elasticum is an autosomal recessive genodermatosis with variable expression, due to mutations in the ABCC6 or ENPP1 gene. It is characterized by elastic fiber mineralization and fragmentation, resulting in skin, eye and cardiovascular symptoms. Significant advances have been made in the last 20 years wi...
journal_title:Cellular signalling
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journal_title:Cellular signalling
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journal_title:Cellular signalling
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journal_title:Cellular signalling
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journal_title:Cellular signalling
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journal_title:Cellular signalling
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journal_title:Cellular signalling
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journal_title:Cellular signalling
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journal_title:Cellular signalling
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journal_title:Cellular signalling
pub_type: 杂志文章
doi:10.1016/j.cellsig.2018.08.009
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journal_title:Cellular signalling
pub_type: 杂志文章
doi:10.1016/j.cellsig.2004.10.015
更新日期:2005-06-01 00:00:00
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journal_title:Cellular signalling
pub_type: 杂志文章
doi:10.1016/0898-6568(94)90049-3
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pub_type: 杂志文章,评审
doi:10.1016/j.cellsig.2008.07.011
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journal_title:Cellular signalling
pub_type: 杂志文章
doi:10.1016/j.cellsig.2008.06.012
更新日期:2008-10-01 00:00:00
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journal_title:Cellular signalling
pub_type: 杂志文章
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journal_title:Cellular signalling
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journal_title:Cellular signalling
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doi:10.1016/j.cellsig.2010.11.017
更新日期:2011-04-01 00:00:00
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journal_title:Cellular signalling
pub_type: 杂志文章
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更新日期:1996-01-01 00:00:00
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journal_title:Cellular signalling
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doi:10.1016/s0898-6568(01)00264-9
更新日期:2002-05-01 00:00:00
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journal_title:Cellular signalling
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doi:10.1016/j.cellsig.2009.12.003
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journal_title:Cellular signalling
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doi:10.1016/j.cellsig.2015.04.006
更新日期:2015-08-01 00:00:00
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journal_title:Cellular signalling
pub_type: 杂志文章
doi:10.1016/j.cellsig.2010.08.012
更新日期:2011-01-01 00:00:00
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journal_title:Cellular signalling
pub_type: 杂志文章
doi:10.1016/j.cellsig.2005.01.003
更新日期:2005-10-01 00:00:00
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journal_title:Cellular signalling
pub_type: 杂志文章
doi:10.1016/s0898-6568(02)00055-4
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journal_title:Cellular signalling
pub_type: 杂志文章
doi:10.1016/j.cellsig.2006.02.008
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