Activation and induction of cytosolic phospholipase A2 by IL-1β in human tracheal smooth muscle cells

Role of MAPKs/p300 and NF-κB

Chiang Wen Lee, I. Ta Lee, Chih Chung Lin, Hui Chun Lee, Wei Ning Lin, Chuen Mao Yang

Research output: Contribution to journalArticle

15 Citations (Scopus)

Abstract

Cytosolic phospholipase A2 (cPLA2) 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 cPLA2 expression and PGE2 synthesis in human tracheal smooth muscle cells (HTSMCs) remain unknown. IL-1β-induced cPLA2 protein and mRNA expression, PGE2 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 cPLA2 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 cPLA2 expression induced by IL-1β. Moreover, p300 was associated with the cPLA2 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 cPLA2 expression and PGE2 secretion.

Original languageEnglish
Pages (from-to)1045-1056
Number of pages12
JournalJournal of Cellular Biochemistry
Volume109
Issue number5
DOIs
Publication statusPublished - Apr 1 2010
Externally publishedYes

Fingerprint

Cytosolic Phospholipases A2
Interleukin-1
Smooth Muscle Myocytes
Muscle
Chemical activation
Cells
Dinoprostone
Transfection
p38 Mitogen-Activated Protein Kinases
Small Interfering RNA
Acetylation
Phosphorylation
Mitogen-Activated Protein Kinase 3
Mitogen-Activated Protein Kinase 1
Arachidonic Acid
Histones
Prostaglandins
Inflammation
Messenger RNA

Keywords

  • Cytosolic phospholipase A
  • IL-1β
  • NF-κB
  • p300
  • PGE

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Activation and induction of cytosolic phospholipase A2 by IL-1β in human tracheal smooth muscle cells : Role of MAPKs/p300 and NF-κB. / Lee, Chiang Wen; Lee, I. Ta; Lin, Chih Chung; Lee, Hui Chun; Lin, Wei Ning; Yang, Chuen Mao.

In: Journal of Cellular Biochemistry, Vol. 109, No. 5, 01.04.2010, p. 1045-1056.

Research output: Contribution to journalArticle

Lee, Chiang Wen ; Lee, I. Ta ; Lin, Chih Chung ; Lee, Hui Chun ; Lin, Wei Ning ; Yang, Chuen Mao. / Activation and induction of cytosolic phospholipase A2 by IL-1β in human tracheal smooth muscle cells : Role of MAPKs/p300 and NF-κB. In: Journal of Cellular Biochemistry. 2010 ; Vol. 109, No. 5. pp. 1045-1056.
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