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

Abstract

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 D₂ (PGD₂) is unknown. In this study, we investigated the effect of PGD₂ on type I collagen secretion in human lung fibroblasts. Pretreatment with PGD₂ (0.1 - 10 μM, 1 h) significantly attenuated type I collagen secretion to the cell supernatant induced by transforming growth factor-β (TGF-β). Although an agonist on chemoattractant receptorhomologous molecule expressed on Th2 cells (CRTH2) did not have any effect, the prostanoid DP-receptor agonist BW245C (0.01 - 1 μM) suppressed TGF-β-induced collagen secretion. PGD₂ and BW245C significantly increased intracellular cAMP level. One-hour pretreatment with forskolin (0.1 - 10 μM), dibutyryl-cAMP (0.01 - 1 mM), and the protein kinase A (PKA)-activator N⁶-phenyl-cyclic AMP (100 μM) significantly reduced TGF-β-induced collagen secretion, while exchange protein activated by cAMP (Epac) activator 8-bromo-2′-O-methyladenosine-3′,5′-cyclic AMP (10 μM) did not affect collagen deposition. These results suggest that PGD₂ inhibits TGF-β-induced collagen secretion via intracellular cAMP accumulation through activating DP receptor.