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TNF‐α‐induced suppressor of cytokine signaling‐3 expression via the JNK1/2, ERK1/2, NADPH oxidase and AP‐1 in human tracheal smooth muscle cells
Author(s) -
Hsu ChihKai,
Yang ChuenMao
Publication year - 2011
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.25.1_supplement.lb408
Subject(s) - apocynin , nadph oxidase , proinflammatory cytokine , small interfering rna , reactive oxygen species , chemistry , microbiology and biotechnology , signal transduction , p38 mitogen activated protein kinases , tumor necrosis factor alpha , transfection , cytokine , intracellular , mapk/erk pathway , inflammation , biology , biochemistry , immunology , gene
Suppressor of cytokine signaling‐3 (SOCS‐3) is an intracellular protein that involves in a wide range of biological processes. Several studies have indicated that SOCS‐3 not only down‐regulates the cytokine‐stimulated signalings, but also exerts anti‐inflammatory responses. However, whether proinflammatory cytokines such as TNF‐α can induce the expression of SOCS‐3 in human tracheal smooth muscle cells (HTSMCs) is still unclear. Here, we report that TNF‐α‐induced SOCS‐3 protein, mRNA expression and promoter activity was attenuated by pretreatment with the inhibitors of JNK1/2 (SP600125), p38 (SB202190), MEK1/2 (U0126), NADPH oxidase [diphenylene iodonium chloride (DPI) and apocynin (APO)], and reactive oxygen species (ROS) scavenger [N‐acetyl‐L‐cysteine (NAC)] or transfection with siRNA. TNF‐α‐stimulated NADPH oxidase/ROS production was attenuated by pretreatment with the inhibitor of JNK1/2, MEK1/2, or NADPH oxidase. The involvement of NF‐κB and AP‐1 in TNF‐α‐induced SOCS‐3 expression was confirmed by the inhibitors of NF‐κB (Bay11‐7082) and AP‐1 (Tanshinone) or transfection with respective siRNAs. Taken together, our results suggested that TNF‐α‐induced NADPH oxidase/ROS production was mediated through the JNK1/2‐ and ERK1/2‐dependent NADPH oxidase pathway, in turn activated AP‐1, and ultimately induced SOCS‐3 expression in HTSMCs.