The effects of PGD2 and DK-PGD2 on features of airway remodeling in human airway epithelial cells and guinea pig lung slices.

Background: Inhibition of prostaglandin (PG)D2 has been demonstrated to reduce inflammation and airway smooth muscle mass in patients with eosinophilic asthma, suggesting that PGD2 not only impacts on airway inflammation, but also on airway remodeling. Thus it is of interest to evaluate the effects of PGD2 on remodeling.Aims: To assess the effects of PGD2 and DK-PGD2 on IL-13-induced goblet cell differentiation of human primary airway epithelial cells in Air Liquid Interface (ALI) cultures as well as on allergen-induced airway remodeling in guinea pig Precision Cut Lung Slices (PCLS).Methods: In vitro experiments were performed by culturing human primary airway epithelial cells in ALI. During differentiation for 14 days, cells were exposed to PGD2 in the absence or presence of IL-13. For ex vivo experiments, guinea pigs were sensitized to ovalbumin and challenged with ovalbumin or saline. PCLS were prepared and exposed to PGD2 or DK-PGD2 in the absence or presence of TGF-β.Results: PGD2 and DK-PGD2 did not affect epithelial barrier function. PGD2 did upregulate MUC5AC but not MUC5B gene expression in ALI cultured primary human epithelial cells. In guinea pig PCLS, PGD2 increased calponin but not sm-MHC protein expression. No effects were observed from DK-PGD2 stimulation.Conclusion: PGD2 may have direct effects on regulating MUC5AC and calponin expression during airway remodeling. These effects are limited, however, and no functional interactions with IL-13 or TGF-β were found. It thus appears that the effects of PGD2 on airway remodeling are the result of both direct and indirect (i.e. by regulating the inflammatory response) effects on airway structural cells