PGE 2 desensitizes β -agonist effect on human lung fibroblast-mediated collagen gel contraction through upregulating PDE4

Qiuhong Fang, Yingmin Ma, Jing Wang, Joel Michalski, Stephen I. Rennard, Xiangde Liu

Research output: Contribution to journalArticle

1 Scopus citations

Abstract

In the current study, we investigated the effect of a long-acting β-agonist (salmeterol) and a phosphodiesterase 4 (PDE4) inhibitor (cilomilast) on human lung fibroblast-mediated collagen gel contraction. Higher concentrations of salmeterol (10-7 and 10-6 M) inhibited fibroblast-mediated collagen gel contraction. No effect was observed with cilomilast alone (up to 10-5 M). In the presence of 10-8 M salmeterol, however, cilomilast could significantly inhibit fibroblast-mediated collagen gel contraction in a concentration-dependent manner (10-7 10-5 M). Blockade of endogenous PGE2 by indomethacin further potentiated the inhibitory effect of salmeterol on fibroblast-mediated collagen gel contraction, but it did not affect cilomilast's effect. Pretreatment with PGE2 abolished the inhibitory effect of salmeterol, but it potentiated the inhibitory effect of cilomilast on fibroblast-mediated collagen gel contraction. Finally, indomethacin slightly inhibited PDE4C expression, while PGE2 stimulated the expression of PDE4A and -4C in human lung fibroblasts. These findings suggest that long-acting β-agonist and PDE4 inhibitor have a synergistic effect in regulating fibroblast tissue repair functions and that PGE2 can modulate the effect of β-agonist and PDE4 inhibitor at least in part through the mechanism of regulating PDE4 expression.

Original languageEnglish (US)
Article number145197
JournalMediators of Inflammation
Volume2013
DOIs
StatePublished - 2013

ASJC Scopus subject areas

  • Immunology
  • Cell Biology

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