In:
Journal of Cellular Biochemistry, Wiley, Vol. 109, No. 5 ( 2010-04), p. 1045-1056
Abstract:
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 IL‐1β. However, the mechanisms underlying IL‐1β‐induced cPLA 2 expression and PGE 2 synthesis in human tracheal smooth muscle cells (HTSMCs) remain unknown. IL‐1β‐induced cPLA 2 protein and mRNA expression, PGE 2 production, or phosphorylation of p42/p44 MAPK, p38 MAPK, and JNK1/2, which was attenuated by pretreatment with the inhibitors of MEK1/2 (U0126), p38 MAPK (SB202190), and JNK1/2 (SP600125) or transfection with siRNAs of MEK1, p42, p38, and JNK2. IL‐1β‐induced cPLA 2 expression was also inhibited by pretreatment with a NF‐κB inhibitor, helenalin or transfection with siRNA of NIK, IKKα, or IKKβ. IL‐β‐induced NF‐κB translocation was blocked by pretreatment with helenalin, but not U0126, SB202190, and SP600125. In addition, transfection with p300 siRNA blocked cPLA 2 expression induced by IL‐1β. Moreover, p300 was associated with the cPLA 2 promoter, which was dynamically linked to histone H4 acetylation stimulated by IL‐1β. These results suggest that in HTSMCs, activation of MAPKs, NF‐κB, and p300 are essential for IL‐1β‐induced cPLA 2 expression and PGE 2 secretion. J. Cell. Biochem. 109: 1045–1056, 2010. © 2010 Wiley‐Liss, Inc.
Type of Medium:
Online Resource
ISSN:
0730-2312
,
1097-4644
Language:
English
Publisher:
Wiley
Publication Date:
2010
detail.hit.zdb_id:
1479976-5
SSG:
12
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