TNF‐α induces cytosolic phospholipase A2 expression via MAPKs and NF‐κ B in human pulmonary alveolar epithelial cells

Abstract

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 A2 (cPLA2) implicated in the pathogenesis of inflammatory diseases. Here, our study aimed to investigate the mechanisms underlying the intracellular signalings involved in cPLA2 expression induced by TNF‐□in human pulmonary alveolar epithelial cells (HPAEpiCs). Western blotting and RT‐PCR analyses showed that TNF‐α‐induced cPLA2 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 cPLA2 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 cPLA2 expression was independently mediated through the activation of MAPKs and NF‐κB pathways.