PGE 2 Desensitizes β -agonist Effect on Human Lung Fibroblast-mediated Collagen Gel Contraction Through Upregulating PDE4

Overview

Journal Mediators Inflamm

Publisher Wiley

Specialties Biochemistry
Pathology

Date 2013 Nov 15

PMID 24227907

Authors

Qiuhong Fang

Yingmin Ma

Jing Wang

Joel Michalski

Stephen I Rennard

Xiangde Liu

Affiliations

Soon will be listed here.

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.

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