title: 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 N(6)-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.
authors.affiliation: Department of Veterinary Pharmacology, Graduate School of Agriculture and Life Sciences, The University of Tokyo, Japan.
authors.forename: Shinya
authors.initials: S
authors.lastname: Ayabe
authors.forename: Taiki
authors.initials: T
authors.lastname: Kida
authors.forename: Masatoshi
authors.initials: M
authors.lastname: Hori
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Ozaki
authors.forename: Takahisa
authors.initials: T
authors.lastname: Murata
mesh_terms: D002478:Cells, Cultured; D003094:Collagen / Q000378:metabolism*; D000242:Cyclic AMP / Q000378:metabolism; D005347:Fibroblasts / Q000378:metabolism*; D006801:Humans; D006827:Hydantoins / Q000494:pharmacology; D008168:Lung / Q000166:cytology* / Q000196:embryology; D015230:Prostaglandin D2 / Q000494:pharmacology* / Q000502:physiology; D011971:Receptors, Immunologic / Q000819:agonists / Q000378:metabolism*; D011982:Receptors, Prostaglandin / Q000819:agonists / Q000378:metabolism*; D016212:Transforming Growth Factor beta / Q000037:antagonists & inhibitors / Q000494:pharmacology
chemical_list: D006827:Hydantoins; D011971:Receptors, Immunologic; D011982:Receptors, Prostaglandin; D016212:Transforming Growth Factor beta; C030669:BW 245C; D003094:Collagen; D000242:Cyclic AMP; D015230:Prostaglandin D2; C036293:prostaglandin D2 receptor