Cigarette smoke extract regulates cytosolic phospholipase A2 expression via NADPH oxidase/MAPKs/AP-1 and p300 in human tracheal smooth muscle cells

Shin Ei Cheng, Chih Chung Lin, I-Ta Lee, Chih Kai Hsu, Yu Ru Kou, Chuen Mao Yang

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19 Citations (Scopus)

Abstract

Up-regulation of cytosolic phospholipase A2 (cPLA2) by cigarette smoke extract (CSE) may play a critical role in airway inflammatory diseases. However, the mechanisms underlying CSE-induced cPLA2 expression in human tracheal smooth muscle cells (HTSMCs) were not completely understood. Here, we demonstrated that CSE-induced cPLA2 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-L-cysteine) or transfection with siRNAs of p47phox 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 p300 and c-Jun complex formation was inhibited by pretreatment with diphenyleneiodonium chloride, apocynin, N-acetyl-L-cysteine or SP600125. These results demonstrated that CSE-induced cPLA2 expression was mediated through NOX2-dependent p42/p44 MAPK and p38 MAPK/c-Fos and JNK1/2/c-Jun/p300 pathways in HTSMCs.

Original languageEnglish
Pages (from-to)589-599
Number of pages11
JournalJournal of Cellular Biochemistry
Volume112
Issue number2
DOIs
Publication statusPublished - Feb 1 2011
Externally publishedYes

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Keywords

  • cigarette smoke extract
  • cytosolic phospholipase A
  • reactive oxygen species
  • signaling transduction
  • tracheal smooth muscle cells

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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