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1 Pulmonary and Critical Care Medicine Section, University of Nebraska Medical Centre, Omaha, Nebraska, USA. 2 Dept of Laboratory Medicine and Respiratory Medicine, Tokyo University, School of Medicine, Tokyo, Japan
CORRESPONDENCE: S.I. Rennard, 985125 Nebraska Medical Centre, Omaha, Nebraska, 68198-5125. Fax: 40 25594878. E-mail: srennard@unmc.edu
Keywords: chemotaxis, fibroblasts, fibronectin, prostaglandin D2
Received: July 9, 2001
Accepted November 7, 2001
This study was funded by the Larson Endowment, University of Nebraska Medical Centre and NIH grant #HL64088-03.
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.
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