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

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

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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
Pages (from-to)99-110
Number of pages12
JournalJournal of Cellular Physiology
Volume210
Issue number1
DOIs
Publication statusPublished - 2007 Jan 1
Externally publishedYes

ASJC Scopus subject areas

  • Physiology
  • Clinical Biochemistry
  • Cell Biology

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    Sugiura, H., Liu, X., Togo, S., Kobayashi, T., Shen, L., Kawasaki, S., Kamio, K., Xing, Q. W., Li, J. M., & Rennard, S. I. (2007). Prostaglandin E2 protects human lung fibroblasts from cigarette smoke extract-induced apoptosis via EP2 receptor activation. Journal of Cellular Physiology, 210(1), 99-110. https://doi.org/10.1002/jcp.20825