Prostaglandin E-2 inhibits fibroblast chemotaxis

Fibroblasts are the major source of extracellular connective tissue matrix, and the recruitment, accumulation, and stimulation of these cells are thou ght to play important roles in both normal healing and the development of f ibrosis. Prostaglandin E-2 (PGE(2)) can inhibit this process by blocking fi broblast proliferation and collagen production. The aim of this study was t o investigate the inhibitory effect of PGE(2) on human plasma fibronectin ( hFN)- and bovine bronchial epithelial cell-conditioned medium (BBEC-CM)-ind uced chemotaxis of human fetal lung fibroblasts (HFL1). Using the Boyden bl ind well chamber technique, PGE(2) (10(-7) M) inhibited chemotaxis to hFN 4 0.8 +/- 5.3% (P < 0.05) and to BBEC-CM 49.7 <plus/minus> 11.7% (P < 0.05). Checkerboard analysis demonstrated inhibition of both chemotaxis and chemok inesis. The effect of PGE(2) was concentration dependent, and the inhibitor y effect diminished with time. Other agents that increased fibroblast cAMP levels, including isoproterenol (10(-5) M), dibutyryl cAMP (10(-5) M), and forskolin (3 x 10(-5) M) had similar effects and inhibited chemotaxis 54.1, 95.3, and 87.0%, respectively. The inhibitory effect of PGE(2) on HFL1 cel l chemotaxis was inhibited by the cAMP-dependent protein kinase (PKA) inhib itor KT-5720, which suggests a cAMP-dependent effect mediated by PKA. In su mmary, PGE(2) appears to inhibit fibroblast chemotaxis, perhaps by modulati ng the rate of fibroblast migration. Such an effect may contribute to regul ation of the wound healing response after injury.