title: Prostaglandin E(2) inhibits fibroblast chemotaxis.
abstract: Fibroblasts are the major source of extracellular connective tissue matrix, and the recruitment, accumulation, and stimulation of these cells are thought to play important roles in both normal healing and the development of fibrosis. Prostaglandin E(2) (PGE(2)) can inhibit this process by blocking fibroblast proliferation and collagen production. The aim of this study was to investigate the inhibitory effect of PGE(2) on human plasma fibronectin (hFN)- and bovine bronchial epithelial cell-conditioned medium (BBEC-CM)-induced chemotaxis of human fetal lung fibroblasts (HFL1). Using the Boyden blind well chamber technique, PGE(2) (10(-7) M) inhibited chemotaxis to hFN 40.8 +/- 5.3% (P < 0.05) and to BBEC-CM 49.7 +/- 11.7% (P < 0.05). Checkerboard analysis demonstrated inhibition of both chemotaxis and chemokinesis. The effect of PGE(2) was concentration dependent, and the inhibitory effect diminished with time. Other agents that increased fibroblast cAMP levels, including isoproterenol (10(-5) M), dibutyryl cAMP (10(-5) M), and forskolin (3 x 10(-5) M) had similar effects and inhibited chemotaxis 54.1, 95.3, and 87.0%, respectively. The inhibitory effect of PGE(2) on HFL1 cell chemotaxis was inhibited by the cAMP-dependent protein kinase (PKA) inhibitor KT-5720, which suggests a cAMP-dependent effect mediated by PKA. In summary, PGE(2) appears to inhibit fibroblast chemotaxis, perhaps by modulating the rate of fibroblast migration. Such an effect may contribute to regulation of the wound healing response after injury.
authors.affiliation: Pulmonary and Critical Care Medicine Section, University of Nebraska Medical Center, Omaha, Nebraska 68198-5125, USA.
authors.forename: T
authors.initials: T
authors.lastname: Kohyama
authors.forename: R F
authors.initials: RF
authors.lastname: Ertl
authors.forename: V
authors.initials: V
authors.lastname: Valenti
authors.forename: J
authors.initials: J
authors.lastname: Spurzem
authors.forename: M
authors.initials: M
authors.lastname: Kawamoto
authors.forename: Y
authors.initials: Y
authors.lastname: Nakamura
authors.forename: T
authors.initials: T
authors.lastname: Veys
authors.forename: L
authors.initials: L
authors.lastname: Allegra
authors.forename: D
authors.initials: D
authors.lastname: Romberger
authors.forename: S I
authors.initials: SI
authors.lastname: Rennard
mesh_terms: D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000818:Animals; D001980:Bronchi / Q000166:cytology / Q000502:physiology; D003994:Bucladesine / Q000494:pharmacology; D002417:Cattle; D002460:Cell Line; D002630:Chemotactic Factors / Q000378:metabolism; D002633:Chemotaxis / Q000187:drug effects*; D005576:Colforsin / Q000494:pharmacology; D017077:Culture Media, Conditioned; D017868:Cyclic AMP-Dependent Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D015237:Dinoprost / Q000494:pharmacology; D015232:Dinoprostone / Q000494:pharmacology*; D005333:Fetus; D005347:Fibroblasts / Q000187:drug effects / Q000502:physiology*; D005353:Fibronectins / Q000378:metabolism; D006801:Humans; D007213:Indomethacin / Q000494:pharmacology; D007545:Isoproterenol / Q000494:pharmacology; D010120:Oxytocics / Q000494:pharmacology; D020545:Respiratory Mucosa / Q000166:cytology* / Q000502:physiology; D013373:Substance P / Q000494:pharmacology; D014660:Vasoactive Intestinal Peptide / Q000494:pharmacology; D014665:Vasodilator Agents / Q000494:pharmacology
chemical_list: D000318:Adrenergic beta-Agonists; D002630:Chemotactic Factors; D017077:Culture Media, Conditioned; D016861:Cyclooxygenase Inhibitors; D005353:Fibronectins; D010120:Oxytocics; D014665:Vasodilator Agents; D005576:Colforsin; D013373:Substance P; D014660:Vasoactive Intestinal Peptide; D003994:Bucladesine; D015237:Dinoprost; D017868:Cyclic AMP-Dependent Protein Kinases; D015232:Dinoprostone; D007545:Isoproterenol; D007213:Indomethacin