Fibroblasts play an important role in the repair and remodelling processes following injury. Prostaglandin D 2 (PGD 2 ) is a potent mediator in inflammatory processes.In this study, the effect of the PGD 2 on human foetal lung fibroblasts (HFL-1) chemotaxis induced by human plasma fibronectin (HFn) was investigated using the blindwell chamber technique.PGD 2 inhibited HFL-1 chemotaxis to HFn (20 mg?mL -1 ) by 20.8¡3.8% (pv0.05). Checkerboard analysis of HFn-directed migration confirmed that PGD 2 inhibited both chemotaxis and chemokinesis. The effect of PGD 2 was concentration-dependent and the inhibitory effect diminished with time. The PGD 2 receptor (DP) agonist BW245C (500 nM) had a similar effect, inhibiting chemotaxis to 39.4¡6.3%. The inhibitory effects of both PGD 2 and BW245C on HFL-1 chemotaxis were blocked by the DP receptor antagonist AH6809 (2 mM). The inhibitory effect of PGD 2 on fibroblast chemotaxis was also blocked by the cyclic adenosine monophosphate (cAMP)-dependent protein kinase (PKA) inhibitor, KT5720, suggesting a DP receptor-initiated, cAMP-dependent effect mediated by PKA.Prostaglandin D 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 following injury in asthma patients.
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