Abstract
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 µg·mL −1 ) by 20.8±3.8% (p 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 µM). 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.
