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Title 

Requirement of hydrogen peroxide generation in TGF-β1 signal transduction in human lung fibroblast cells: involvement of hydrogen peroxide and Ca2+ in TGF-β1-induced IL-6 expression

Authors 

Eun Sung JunnKee Nyung LeeHyang Ran JuSeung Hyun HanJoo Young ImHyung Sik KangTae Ho LeeYun Soo BaeKwon Soo HaZee Won LeeSue Goo RheeIn Pyo Choi

Publisher 

American Association of Immunologists

Issue Date 

2000

Citation 

Journal of Immunology, vol. 165, no. 4, pp. 2190-2197

Keywords 

hydrogen peroxidetransforming growth factor beta1cell stimulationhumanhuman celllung fibroblastsignal transductionfibroblastshumans

Abstract 

Stimulation of human lung fibroblast cells with TGF-β1 resulted in a transient burst of reactive oxygen species with maximal increase at 5 min after treatment. This reactive oxygen species increase was inhibited by the antioxidant, N-acetyl-L-cysteine (NAC). TGF-β1 treatment stimulated IL-6 gene expression and protein synthesis in human lung fibroblast cells. Antioxidants including NAC, glutathione, and catalase reduced TGF-β1-induced IL-6 gene expression, and direct H2O2 treatment induced IL-6 expression in a dose-dependent manner. NAC also reduced TGF-β1-induced AP-1 binding activity, which is involved in IL-6 gene expression. It has been reported that Ca2+ influx is stimulated by TGF-β1 treatment. EGTA suppressed TGF- β1- or H2O2- induced IL-6 expression, and ionomycin increased IL-6 expression, with simultaneously modulating AP-1 activity in the same pattern. PD98059, an inhibitor of mitogen-activated protein kinase (MAPK) kinase/extracellular signal-related kinase kinase 1, suppressed TGF-β1- or H2O2-induced IL-6 and AP-1 activation. In addition, TGF-β1 or H2O2 increased MAPK activity which was reduced by EGTA and NAC, suggesting that MAPK is involved in TGF-β1-induced IL-6 expression. Taken together, these results indicate that TGF-β1 induces a transient increase of intracellular H2O2 production, which regulates downstream events such as Ca2+ influx, MAPK, and AP-1 activation and IL-6 gene expression.

ISSN 

0022-1767

Appears in Collections

1. Journal Articles > Journal Articles

Registered Date

2017-04-19


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