Prostaglandin E2 protects human lung fibroblasts from cigarette smoke extract-induced apoptosis via EP2 receptor activation

Hisatoshi Sugiura, Xiang-de Liu, Shinsaku Togo, Tetsu Kobayashi, Lei Shen, Shin Kawasaki, Koichiro Kamio, Qi Wang Xing, Jun Mao Li, Stephen I. Rennard

Research output: Contribution to journalArticle

22 Citations (Scopus)

Abstract

Prostaglandin E2 (PGE2) has been shown to have a strong cytoprotective effect, inhibiting apoptosis. In the present study, we evaluated whether PGE2 has a protective effect on cigarette smoke extract (CSE)-induced apoptosis in human lung fibroblasts. Apoptosis was assessed by various methods, including DNA content analysis. CSE (15%-20%) led to apoptosis and induced imbalance in favor of pro- over anti-apoptotic protein expression and activated caspases. PGE2 blocked CSE-induced apoptosis and modulated the balance of pro- and anti-apoptotic proteins and decreased the activation of caspases. This anti-apoptotic effect was mediated via EP 2 receptor activation as the EP2 agonist butaprost mimicked PGE2 activity and siRNA for the EP2 receptor blocked it. An adenylyl cyclase inhibitor was found to abolish the PGE 2-mediated cytoprotective effect. Correspondingly, c-AMP analogs blocked CSE-induced apoptosis. Consistently, the protein kinase A (PKA) inhibitor KT-5720 abolished PGE2-mediated protection. PGE2 and butaprost phosphorylated Bad and KT-5720 blocked phosphorylation. These results suggest that PGE2 inhibits CSE-induced apoptosis via EP 2 receptor activation and activation of PKA, which leads to an alteration in the balance between pro-and anti-apoptotic factors. Through such a mechanism, PGE2 may alter survival of cells in the smoke-exposed lungs, thus affecting the pathogenesis of cigarette smoke-induced disease.

Original languageEnglish (US)
Pages (from-to)99-110
Number of pages12
JournalJournal of Cellular Physiology
Volume210
Issue number1
DOIs
StatePublished - Jan 1 2007

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Fibroblasts
Dinoprostone
Smoke
Tobacco Products
Chemical activation
Apoptosis
Lung
Apoptosis Regulatory Proteins
Caspases
Cyclic AMP-Dependent Protein Kinases
Phosphorylation
Adenosine Monophosphate
Protein Kinase Inhibitors
Prostaglandins E
Adenylyl Cyclases
Small Interfering RNA
Cell Survival
Cells
DNA

ASJC Scopus subject areas

  • Physiology
  • Clinical Biochemistry
  • Cell Biology

Cite this

Prostaglandin E2 protects human lung fibroblasts from cigarette smoke extract-induced apoptosis via EP2 receptor activation. / Sugiura, Hisatoshi; Liu, Xiang-de; Togo, Shinsaku; Kobayashi, Tetsu; Shen, Lei; Kawasaki, Shin; Kamio, Koichiro; Xing, Qi Wang; Li, Jun Mao; Rennard, Stephen I.

In: Journal of Cellular Physiology, Vol. 210, No. 1, 01.01.2007, p. 99-110.

Research output: Contribution to journalArticle

Sugiura, H, Liu, X, Togo, S, Kobayashi, T, Shen, L, Kawasaki, S, Kamio, K, Xing, QW, Li, JM & Rennard, SI 2007, 'Prostaglandin E2 protects human lung fibroblasts from cigarette smoke extract-induced apoptosis via EP2 receptor activation', Journal of Cellular Physiology, vol. 210, no. 1, pp. 99-110. https://doi.org/10.1002/jcp.20825
Sugiura, Hisatoshi ; Liu, Xiang-de ; Togo, Shinsaku ; Kobayashi, Tetsu ; Shen, Lei ; Kawasaki, Shin ; Kamio, Koichiro ; Xing, Qi Wang ; Li, Jun Mao ; Rennard, Stephen I. / Prostaglandin E2 protects human lung fibroblasts from cigarette smoke extract-induced apoptosis via EP2 receptor activation. In: Journal of Cellular Physiology. 2007 ; Vol. 210, No. 1. pp. 99-110.
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