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TNF‐α induces cytosolic phospholipase A 2 expression via MAPKs and NF‐κ B in human pulmonary alveolar epithelial cells
Author(s) -
Hsiao YuChun,
Yang ChuenMao
Publication year - 2010
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.24.1_supplement.963.3
Subject(s) - proinflammatory cytokine , tumor necrosis factor alpha , p38 mitogen activated protein kinases , mapk/erk pathway , microbiology and biotechnology , nf κb , small interfering rna , kinase , a549 cell , transfection , biology , nfkb1 , signal transduction , iκbα , phosphorylation , chemistry , inflammation , cancer research , immunology , cell culture , cell , biochemistry , transcription factor , genetics , gene
Exposure of human pulmonary alveolar epithelial cells to external insults triggers inflammatory processes in the respiratory system. Elevated levels of proinflammatory cytokines, such as tumor necrosis factor‐α (TNF‐α) have been found in the airway fluids, which may induce up‐regulation of cytosolic phospholipase A 2 (cPLA 2 ) implicated in the pathogenesis of inflammatory diseases. Here, our study aimed to investigate the mechanisms underlying the intracellular signalings involved in cPLA 2 expression induced by TNF‐□in human pulmonary alveolar epithelial cells (HPAEpiCs). Western blotting and RT‐PCR analyses showed that TNF‐α‐induced cPLA 2 protein and mRNA expression as well as phosphorylation of p42/p44 MAPK, p38 MAPK, and JNK were attenuated by pretreatment with the inhibitors of MEK1/2 (PD98059), p38 MAPK (SB202190), and JNK1/2 (SP600125) or transfection with siRNAs of p42, p38, and JNK2. Furthermore, TNF‐α‐induced cPLA 2 expression was inhibited by a selective NF‐κB inhibitor (Bay11‐7082), consistent with that TNF‐α stimulated both IκBα degradation and NF‐κB translocation in these cells. TNF‐α‐induced NF‐κB translocation was blocked by pretreatment with Bay11‐7082, but not by PD98059, SB202190, and SP600125. These results suggested that in HPAEpiCs, TNF‐α‐induced cPLA 2 expression was independently mediated through the activation of MAPKs and NF‐κB pathways.