Prostaglandin D-2 induces IL-8 and GM-CSF by bronchial epithelial cells in a CRTH2-independent pathway

Background: Prostaglandin D-2 (PGD(2)), a major prostanoid produced by activated mast cells, has long been implicated in allergic diseases. PGD2 demonstrates its effects through two G-protein-coupled receptors, DP and CRTH2. The PGD(2)/CRTH2 system mediates chernotaxis of eosinophils, basophils, and Th2 cells, which are involved in the induction of allergic inflammation. Although recent studies have shown that the specific receptors for PGD2, DP, and CRTH2 are expressed in various human tissues, the role of PGD2 is unknown in human bronchial epithelial cells. In this study, we investigated the expression and function of CRTH2/DP on NCI-H-292 and NHBE cells. Method: The CRTH2/DP expression was examined by RT-PCR and flow-cytometric analysis. NCIH292 and NHBE cells were cultured in the presence of various stimulants. The resulting supernatants were measured by ELISA. Results: We demonstrated that PGD2 induced production of IL-8 and GM-CSF in NCI-H-292 and NHBE cells. DK-PGD2 (CRTH2 agonist) and latanoprost (FP, a prostaglandin F receptor, agonist) failed to augment the production of these cytokines. Pretreatment with ramatroban (CRTH2 antagonist) and AL8810 (FP antagonist) did not reduce the production of these cytokines. The PGD2-induced cytokine production was inhibited by pertussis toxin or specific inhibitors for MAP/ERK kinase (PD98059) and p38 MAP kinase (S13202190). Conclusion: These results suggest that PGD(2) is a potent inducer of IL-8 and GM-CSF production with MAP/ERK and p38 MAP kinase activation, but this is independent of CRTH2 activation. Copyright (c) 2006 S. Karger AG, Basel.