Prostacyclin analogs inhibit fibroblast migration

Tadashi Kohyama, Xiangde Liu, Hui Jung Kim, Tetsu Kobayashi, Ronald F. Ertl, Fu Qiang Wen, Hajime Takizawa, Stephen I. Rennard

Research output: Contribution to journalArticlepeer-review

30 Scopus citations

Abstract

The controlled accumulation of fibroblasts to sites of inflammation is crucial to effective tissue repair after injury. Either inadequate or excessive accumulation of fibroblasts could result in abnormal tissue function. Prostacyclin (PGI2) is a potent mediator in the coagulation and inflammatory processes. The aim of this study was to investigate the effect of PGI2 on chemotaxis of human fetal lung fibroblasts (HFL-1). Using the blind well chamber technique, we found that the PGI2 analog carbaprostacyclin (10-6 M) inhibited HFL-1 chemotaxis to human plasma fibronectin (20 μg/ml) 58.0 ± 13.2% (P < 0.05) and to platelet-derived growth factor (PDGF)-BB (10 ng/ml) 48.7 ± 4.6% (P < 0.05). Checkerboard analysis demonstrated that carbaprostacyclin inhibits both directed and undirected migration. The inhibitory effect of the carbaprostacyclin was concentration dependent and blocked by the cAMP-dependent protein kinase (PKA) inhibitor KT-5720, suggesting that a cAMP-PKA pathway may be involved in the process. Two other PGI2 analogs, ciprostene and dehydro-15-cyclohexyl carbaprostacyclin (both 10-6 M), significantly inhibited fibroblast migration to fibronectin. In summary, PGI2 appears to inhibit fibroblast chemotaxis to fibronectin and PDGF-BB. Such an effect may contribute to the regulation of fibroblasts in wound healing and could contribute to the pathogenesis of diseases characterized by abnormal tissue repair remodeling.

Original languageEnglish (US)
Pages (from-to)L428-L432
JournalAmerican Journal of Physiology - Lung Cellular and Molecular Physiology
Volume283
Issue number2 27-2
DOIs
StatePublished - 2002

Keywords

  • Inflammation
  • Prostaglandin I
  • Protein kinase
  • Tissue repair

ASJC Scopus subject areas

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

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