Thy-1 attenuates TNF-alpha-activated gene expression in mouse embryonic fibroblasts via Src family kinase.

PloS One
Bin ShanJoseph A Lasky

Abstract

Heterogeneous surface expression of Thy-1 in fibroblasts modulates inflammation and may thereby modulate injury and repair. As a paradigm, patients with idiopathic pulmonary fibrosis, a disease with pathologic features of chronic inflammation, demonstrate an absence of Thy-1 immunoreactivity within areas of fibrotic activity (fibroblast foci) in contrast to the predominant Thy-1 expressing fibroblasts in the normal lung. Likewise, Thy-1 deficient mice display more severe lung fibrosis in response to an inflammatory injury than wildtype littermates. We investigated the role of Thy-1 in the response of fibroblasts to the pro-inflammatory cytokine TNF-alpha. Our study demonstrates distinct profiles of TNF-alpha-activated gene expression in Thy-1 positive (Thy-1+) and negative (Thy-1-) subsets of mouse embryonic fibroblasts (MEF). TNF-alpha induced a robust activation of MMP-9, ICAM-1, and the IL-8 promoter driven reporter in Thy-1- MEFs, in contrast to only a modest increase in Thy-1+ counterparts. Consistently, ectopic expression of Thy-1 in Thy-1- MEFs significantly attenuated TNF-alpha-activated gene expression. Mechanistically, TNF-alpha activated Src family kinase (SFK) only in Thy-1- MEFs. Blockade of SFK activation abrogate...Continue Reading

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Citations

May 15, 2013·Journal of Hematology & Oncology·Yan ZhuangBin Shan
Dec 17, 2011·The American Journal of the Medical Sciences·Viranuj SueblinvongJesse Roman
Jul 28, 2015·Laboratory Investigation; a Journal of Technical Methods and Pathology·Shunpeng XingZhengyu He
May 18, 2011·Laboratory Investigation; a Journal of Technical Methods and Pathology·Gustavo RamírezAnnie Pardo
Jul 23, 2014·The Journal of Pharmacology and Experimental Therapeutics·Meng HuQiang Ding
Nov 25, 2014·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Collynn F WoellerRichard P Phipps
Feb 28, 2019·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Anja Saalbach, Ulf Anderegg

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Datasets Mentioned

BETA
BC011106
BC046991

Methods Mentioned

BETA
transfection
zymography
light microscopy
transfections
Assay
FACS
immunoprecipitation
phosphotransferase

Software Mentioned

AlphaEase StandAlone
GraphPad
GraphPad Prism

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