期刊
JOURNAL OF CELLULAR BIOCHEMISTRY
卷 112, 期 2, 页码 589-599出版社
WILEY
DOI: 10.1002/jcb.22949
关键词
CIGARETTE SMOKE EXTRACT; TRACHEAL SMOOTH MUSCLE CELLS; REACTIVE OXYGEN SPECIES; SIGNALING TRANSDUCTION; CYTOSOLIC PHOSPHOLIPASE A2
资金
- National Science Council, Taiwan [NSC98-2314-B-182-021-MY3, NSC96-2320-B-182-003, NSC96-2320-B-182-047-MY3]
- Chang Gung Medical Research Foundation, Taiwan [CMRPD32043, CMRPD170332, CMRPG381522, CMRPG350653, CMRPG360513]
Up-regulation of cytosolic phospholipase A(2) (cPLA(2)) by cigarette smoke extract (CSE) may play a critical role in airway inflammatory diseases. However, the mechanisms underlying CSE-induced cPLA(2) expression in human tracheal smooth muscle cells (HTSMCs) were not completely understood. Here, we demonstrated that CSE-induced cPLA(2) protein and mRNA expression was inhibited by pretreatment with the inhibitors of AP-1 (tanshinone IIA) and p300 (garcinol) or transfection with siRNAs of c-Jun, c-Fos, and p300. Moreover, CSE also induced c-Jun and c-Fos expression, which were inhibited by pretreatment with the inhibitors of NADPH oxidase (diphenyleneiodonium chloride and apocynin) and the ROS scavenger (N-acetyl-t-cysteine) or transfection with siRNAs of p47(phox) and NADPH oxidase (NOX)2. CSE-induced c-Fos expression was inhibited by pretreatment with the inhibitors of MEK1 (U0126) and p38 MAPK (SB202190) or transfection with siRNAs of p42 and p38. CSE-induced c-Jun expression and phosphorylation were inhibited by pretreatment with the inhibitor of JNK1/2 (SP600125) or transfection with JNK2 siRNA. CSE-stimulated p300 phosphorylation was inhibited by pretreatment with the inhibitors of NADPH oxidase and JNK1/2. Furthermore, CSE-induced 1)300 and c-Jun complex formation was inhibited by pretreatment with diphenyleneiodonium chloride, apocynin, N-acetyl-t-cysteine or SP600125. These results demonstrated that CSE-induced cPLA(2) expression was mediated through NOX2-dependent p42/p44 MAPK and p38 MAPK/c-Fos and JNK1/2/c-Jun/p300 pathways in HTSMCs. J. Cell. Biochem. 112: 589-599, 2011. (C) 2010 Wiley-Liss, Inc.
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