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Plos One : Tnf-α Induces Cytosolic Phospholipase A2 Expression in Human Lung Epithelial Cells Via Jnk1, Volume 8

By Liu, Guangwei

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Book Id: WPLBN0003968746
Format Type: PDF eBook :
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Reproduction Date: 2015

Title: Plos One : Tnf-α Induces Cytosolic Phospholipase A2 Expression in Human Lung Epithelial Cells Via Jnk1, Volume 8  
Author: Liu, Guangwei
Volume: Volume 8
Language: English
Subject: Journals, Science, Medical Science
Collections: Periodicals: Journal and Magazine Collection
Historic
Publication Date:
Publisher: Plos

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Liu, G. (n.d.). Plos One : Tnf-α Induces Cytosolic Phospholipase A2 Expression in Human Lung Epithelial Cells Via Jnk1, Volume 8. Retrieved from http://worldebookfair.com/


Description
Description : Background : Cytosolic phospholipase A2 (cPLA2) plays a pivotal role in mediating agonist-induced arachidonic acid (AA) release for prostaglandin (PG) synthesis during inflammation triggered by tumor necrosis factor-a (TNF-a). However, the mechanisms underlying TNF-a-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 PGE2 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-a markedly stimulated p42/p44 MAPK, p38 MAPK, and JNK1/2 phosphorylation which were attenuated by their respective inhibitors. In addition, TNF-a also stimulated c-Jun and ATF2 phosphorylation which were inhibited by pretreatment with SP600125 and SB202190, respectively, but not PD98059. Furthermore, TNF-a-induced cPLA2 promoter activity was abrogated by transfection with the point-mutated AP-1 cPLA2 construct. Finally, we showed that TNF-a time-dependently induced p300/c-Fos/c-Jun/ATF2 complex formation in HPAEpiCs. On the other hand, TNF-a 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-a 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-a-induced cPLA2 expression was mediated through p38 MAPK- and JNK1/2-dependent p300/c-Fos/c-Jun/ATF2 complex formation in HPAEpiCs.

 

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