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Requirement of hydrogen peroxide generation in TGF-beta 1 signal transduction in human lung fibroblast cells: Involvement of hydrogen peroxide and Ca2+ in TGF-beta 1-induced IL-6 expression

Title
Requirement of hydrogen peroxide generation in TGF-beta 1 signal transduction in human lung fibroblast cells: Involvement of hydrogen peroxide and Ca2+ in TGF-beta 1-induced IL-6 expression
Authors
Junn, ELee, KNJu, HRHan, SHIm, JYKang, HSLee, THBae, YSHa, KSLee, ZWRhee, SGChoi, I
Ewha Authors
배윤수
SCOPUS Author ID
배윤수scopus
Issue Date
2000
Journal Title
JOURNAL OF IMMUNOLOGY
ISSN
0022-1767JCR Link
Citation
vol. 165, no. 4, pp. 2190 - 2197
Publisher
AMER ASSOC IMMUNOLOGISTS
Indexed
SCI; SCIE; SCOPUS WOS
Abstract
Stimulation of human lung fibroblast cells with TGF-beta 1 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-beta 1 treatment stimulated IL-6 gene expression and protein synthesis in human lung fibroblast cells. Antioxidants including NAC, glutathione, and catalase reduced TGF-beta 1-induced IL-6 gene expression, and direct H2O2 treatment induced IL-6 expression in a dose-dependent manner. NAC also reduced TGF-beta 1-induced AP-1 binding activity, which is involved in IL-6 gene expression. It has been reported that Ca2+ influx is stimulated by TGF-beta 1 treatment. EGTA suppressed TGF-beta 1- 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-beta 1- or H2O2-induced IL-6 and AP-1 activation. In addition, TGF-beta 1 or H2O2 increased MAPK activity which was reduced by EGTA and NAG, suggesting that MAPK is involved in TGF-beta 1-induced IL-6 expression. Taken together, these results indicate that TGF-beta 1 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.
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자연과학대학 > 생명과학전공 > Journal papers
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