PGD2 modulates fibroblast-mediated native collagen gel contraction

Tadashi Kohyama, Todd A. Wyatt, Xiangde Liu, Fu Qiang Wen, Tetsu Kobayashi, Qiuhong Fang, Jung Kim Hui, Stephen I. Rennard

Research output: Contribution to journalArticle

19 Scopus citations

Abstract

Repair of tissues is a necessary step in restoring tissue function following injury consequent to inflammation. Many inflammatory mediators are capable of modulating not only the activity of "inflammatory cells" but also of modulating functions of parenchymal cells that may contribute to repair. Disordered repair is believed to contribute to tissue dysfunction in many inflammatory diseases, including bronchial asthma. The current study evaluated the ability of prostaglandin D2 (PGD2) to modulate fibroblast repair using the in vitro contraction of three-dimensional native collagen gels as a model system. PGD2 stimulated gel contraction in a concentration- and time-dependent manner. In contrast, the PGD2 analog BW245C inhibited contraction. Both effects were blocked by a DP-receptor blocker (AH6809). Neither TP receptor blocker SQ29548 nor protein kinase (PK) A antagonist KT5720 hand an effect on PGD2-stimulated contraction, suggesting action through a novel prostaglandin D receptor. PKC inhibitor calphostin-C (10-6 M) blocked the PGD2 stimulation of gel contraction. A calcium-independent PKC-ε inhibitor (Ro31-8220), but not calcium-dependent PKC-α and -β inhibitors, also blocked the PGD2 effect on contraction, implying a role for a calcium-independent pathway. This study, therefore, supports a role for PGD2 in tissue repair and remodeling. These effects of PGD2 appear to be mediated through receptor-signal transduction pathways different from the cAMP-PKA pathways mediating the proinflammatory activity of PGD2, creating the possibility for selective therapeutic manipulation.

Original languageEnglish (US)
Pages (from-to)375-381
Number of pages7
JournalAmerican journal of respiratory cell and molecular biology
Volume27
Issue number3
DOIs
StatePublished - Sep 2002

ASJC Scopus subject areas

  • Molecular Biology
  • Pulmonary and Respiratory Medicine
  • Clinical Biochemistry
  • Cell Biology

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