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
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- 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
- Eun Sung Junn; Kee Nyung Lee; Hyang Ran Ju; Seung Hyun Han; Joo Young Im; Hyung Sik Kang; Tae Ho Lee; Yun Soo Bae; Kwon Soo Ha; Zee Won Lee; Sue Goo Rhee; In Pyo Choi
- Bibliographic Citation
- Journal of Immunology, vol. 165, no. 4, pp. 2190-2197
- Publication Year
- 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.
- Amer Assoc Immunologists
- Appears in Collections:
- Division of Biomedical Research > Personalized Genomic Medicine Research Center > 1. Journal Articles
Division of Biomedical Research > Immunotherapy Research Center > 1. Journal Articles
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