关键词: 关键词：前列腺素受体2, 黏蛋白, 炎症因子, 信号转导

Abstract: Objective To investigate the effect of D prostanoid receptor 2 （DP2） on mucin (MUC) 5AC overexpression induced by prostaglandin D2（PGD2）and the potential mechanism． Methods The human airway epithelial（16HBE）cells were stimulated with PGD2 (1 μmol/L). In intervention experiments, cells were pretreated with DP2 antagonist AZD6430, DP1 antagonist BWA868C and PI3K specific inhibitor LY294002. Then, PGD2 stimulation was used. Cells were divided into 6 groups: control group ( incubated in DEME / Ham's F12 medium without fetal bovine serum), PGD2 stimulation group, PGD2 stimulation+AZD6430 group, PGD2 stimulation+BWA868C group, PGD2 stimulation +LY294002 group. The levels of tumor necrosis factor (TNF)-α, interleukin (IL)- 4 and IL-13 protein were tested by real-time PCR and ELISA, respectively. MUC5AC protein level was assessed by immunofluorescence. Western blot was used to detected the levels of DP2, DP1, PI3K and phosphorylation of AKT (p-AKT). MUC5AC mRNA expression was tested by real-time PCR. Results PGD2 caused a obversely increase of MUC5AC, TNF-α, IL-4, IL-13, DP2, PI3K and p-AKT when compared with normal control group (P<0.05). Inhibited of DP2 activity, production of TNF-α, IL-4, IL-13, MUC5AC, PI3K and p-AKT were significantly lower than that of PGD2 stimulation group (P<0.05). The level of TNF-α，IL-4, IL-13 and MUC5AC mRAN and protein expression were also attenuated after treatment with LY294002 (P<0.05). Conclusion Our study suggests that DP2 mediates mucus hypersecretion induced by PGD2 via PI3K/AKT pathway.

Key words: Key words: prostaglandin receptor 2, mucin , inflammatory cytokines, signal transduction