Prostaglandin E2 inhibits fibroblast chemotaxis

Tadashi Kohyama, Ronald F. Ertl, Vincenzo Valenti, John Spurzem, Masashi Kawamoto, Yoichi Nakamura, Tom Veys, Luigi Allegra, Debra Romberger, Stephen I. Rennard

Research output: Contribution to journalArticle

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 E2 (PGE2) can inhibit this process by blocking fibroblast proliferation and collagen production. The aim of this study was to investigate the inhibitory effect of PGE2 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, PGE2 (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 PGE2 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 × 10-5 M) had similar effects and inhibited chemotaxis 54.1, 95.3, and 87.0%, respectively. The inhibitory effect of PGE2 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, PGE2 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.

Original languageEnglish
JournalAmerican Journal of Physiology - Lung Cellular and Molecular Physiology
Volume281
Issue number5 25-5
Publication statusPublished - 2001

Keywords

  • Adenosine 3′,5′-cyclic monophosphate
  • Eicosanoids
  • Fibronectin
  • Fibrosis
  • Repair

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine
  • Cell Biology
  • Physiology
  • Physiology (medical)

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