Document Type
Article
Journal Title
Mediators of Inflammation
Publication Date
2013
Volume
2013
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.
MeSH Headings
Adrenergic beta-2 Receptor Agonists, Albuterol, Anti-Inflammatory Agents, Non-Steroidal, Collagen, Cyclic Nucleotide Phosphodiesterases, Type 4, Cyclohexanecarboxylic Acids, Dinoprostone, Fibroblasts, Gels, Gene Expression Regulation, Humans, Indomethacin, Lung, Nitriles, Phosphodiesterase 4 Inhibitors, Pulmonary Disease, Chronic Obstructive, Salmeterol Xinafoate, Up-Regulation
DOI Link
ISSN
1466-1861
Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 International License.
Recommended Citation
Fang, Qiuhong; Ma, Yingmin; Wang, Jing; Michalski, Joel; Rennard, Stephen I.; and Liu, Xiangde, "PGE 2 Desensitizes β -Agonist Effect on Human Lung Fibroblast-Mediated Collagen Gel Contraction Through Opregulating PDE4" (2013). Journal Articles: Pulmonary & Critical Care Med. 70.
https://digitalcommons.unmc.edu/com_pulm_articles/70
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