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Cigarette smoke induces cPLA2 expression via NADPH oxidase, MAPKs, AP‐1 and NF‐κB in human airway smooth muscle cells
Author(s) -
Cheng ShinEi,
Jou MeiJie,
Kou YuRu,
Yang ChuenMao
Publication year - 2008
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.22.1_supplement.897.1
Subject(s) - nadph oxidase , p38 mitogen activated protein kinases , small interfering rna , transfection , mapk/erk pathway , chemistry , nf κb , phosphorylation , inflammation , oxidase test , microbiology and biotechnology , reactive oxygen species , signal transduction , biology , biochemistry , immunology , enzyme , gene
Cigarette smoking (CS) causes a variety of airway inflammatory diseases, including chronic obstructive pulmonary disease and asthma. After allergens stimulation, increased of cPLA 2 expression may play a critical role in airway inflammation. However, the mechanisms underlying CS‐induced cPLA 2 expression in airway smooth muscle cells (ASMCs) are still unknown. In this study, CS‐induced NADPH oxidase activation and superoxide production, led to increase cPLA 2 expression in human ASMCs. The mechanism of cPLA 2 expression is dependent on MAPKs phosphorylation, NF‐κB and AP‐1 activation. Pretreatment with the inhibitors of NADPH oxidase (DPI, apocyanin), N ‐acetylcysteine, MEK1/2 (UO126), p38 MAPK (SB202190), and JNK (SP600125) suppressed CS‐induced cPLA 2 expression, revealed by RT‐PCR and Western blotting analyses. Transfection with siRNAs of JNK1, p42 and p38 also reduced cPLA 2 expression. Induction of cPLA 2 by CS was inhibited by a NF‐κB inhibitor (helenalin) and a selective inhibitor of AP‐1 (curcumin). Moreover, promoter assays revealed that increases of cPLA 2 , NF‐κB and AP‐1 luciferase activities in response to CS were attenuated by these inhibitors. These results suggested that in ASMCs, activation of NADPH oxidase, MAPKs pathway, NF‐κB, and AP‐1 is essential for CS‐induced cPLA 2 expression.