Prostaglandin D₂ inhibits fibroblast migration

Fibroblasts play an important role in the repair and remodelling processes following injury. Prostaglandin D₂ (PGD₂) is a potent mediator in inflammatory processes. In this study, the effect of the PGD₂ on human foetal lung fibroblasts (HFL-1) chemotaxis induced by human plasma fibronectin (HFn) was investigated using the blindwell chamber technique. PGD₂ inhibited HFL-1 chemotaxis to HFn (20 μg·mL^-1) by 20.8±3.8% (p<0.05). Checkerboard analysis of HFn-directed migration confirmed that PGD₂ inhibited both chemotaxis and chemokinesis. The effect of PGD₂ was concentration-dependent and the inhibitory effect diminished with time. The PGD₂ receptor (DP) agonist BW245C (500 nM) had a similar effect, inhibiting chemotaxis to 39.4±6.3%. The inhibitory effects of both PGD₂ and BW245C on HFL-1 chemotaxis were blocked by the DP receptor antagonist AH6809 (2 μM). The inhibitory effect of PGD₂ 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 D₂ 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.