被撤回的出版物: TNF-α Induces Cytosolic Phospholipase A2 Expression in Human Lung Epithelial Cells via JNK1/2-and p38 MAPK-Dependent AP-1 Activation (Retracted article. See vol. 17, 2022)

Background: Cytosolic phospholipase A(2) (cPLA(2)) plays a pivotal role in mediating agonist-induced arachidonic acid (AA) release for prostaglandin (PG) synthesis during inflammation triggered by tumor necrosis factor-alpha (TNF-alpha). However, the mechanisms underlying TNF-alpha-induced cPLA2 expression in human lung epithelial cells (HPAEpiCs) were not completely understood. Principal Findings: We demonstrated that TNF-a induced cPLA2 mRNA and protein expression, promoter activity, and PGE(2) secretion in HPAEpiCs. These responses induced by TNF-a were inhibited by pretreatment with the inhibitor of MEK1/2 (PD98059), p38 MAPK (SB202190), JNK1/2 (SP600125), or AP-1 (Tanshinone IIA) and transfection with siRNA of TNFR1, p42, p38, JNK2, c-Jun, c-Fos, or ATF2. We showed that TNF-alpha markedly stimulated p42/p44 MAPK, p38 MAPK, and JNK1/2 phosphorylation which were attenuated by their respective inhibitors. In addition, TNF-alpha also stimulated c-Jun and ATF2 phosphorylation which were inhibited by pretreatment with SP600125 and SB202190, respectively, but not PD98059. Furthermore, TNF-alpha-induced cPLA2 promoter activity was abrogated by transfection with the point-mutated AP-1 cPLA2 construct. Finally, we showed that TNF-alpha time-dependently induced p300/c-Fos/c-Jun/ATF2 complex formation in HPAEpiCs. On the other hand, TNF-alpha induced in vivo binding of c-Jun, c-Fos, ATF2, and p300 to the cPLA2 promoter in these cells. In an in vivo study, we found that TNF-alpha induced leukocyte count in BAL fluid of mice and cPLA2 mRNA levels in lung tissues via MAPKs and AP-1. Significance: Taken together, these results demonstrated that TNF-alpha-induced cPLA2 expression was mediated through p38 MAPK-and JNK1/2-dependent p300/c-Fos/c-Jun/ATF2 complex formation in HPAEpiCs.