Prostaglandin D2 Inhibits Collagen Secretion From Lung Fibroblasts by Activating the DP Receptor

Lung fibroblasts are responsible for collagen secretion during normal tissue repair and the development of fibrosis. Many other prostaglandins have been reported to regulate collagen synthesis in lung fibroblasts, but the role of prostaglandin D-2 (PGD(2)) is unknown. In this study, we investigated the effect of PGD(2) on type I collagen secretion in human lung fibroblasts. Pretreatment with PGD(2) (0.1-10 mu M, 1 h) significantly attenuated type I collagen secretion to the cell supernatant induced by transforming growth factor-beta (TGF-beta) Although an agonist on chemoattractant receptor-homologous molecule expressed on Th2 cells (CRTH2) did not have any effect, the prostanoid DP-receptor agonist BW245C (0.01 - 1 mu M) suppressed TGF-beta-induced collagen secretion. PGD(2) and BW245C significantly increased intracellular cAMP level. One-hour pretreatment with forskolin (0.1 - 10 mu M), dibutyryl-cAMP (0.01 - 1 mM), and the protein kinase A (PKA)-activator N-6-phenyl-cyclic AMP (100 mu M) significantly reduced TGF-beta-induced collagen secretion, while exchange protein activated by cAMP (Epac) activator 8-bromo-2'-O-methyladenosine-3',5'-cyclic AMP (10 mu M) did not affect collagen deposition. These results suggest that PGD(2) inhibits TGF-beta-induced collagen secretion via intracellular cAMP accumulation through activating DP receptor.