RT Journal Article
SR Electronic
T1 The effects of PGD2 and DK-PGD2 on features of airway remodeling in human airway epithelial cells and guinea pig lung slices
JF European Respiratory Journal
JO Eur Respir J
FD European Respiratory Society
SP 1418
DO 10.1183/13993003.congress-2020.1418
VO 56
IS suppl 64
A1 Rahmawati, Siti Farah
A1 Verschut, Vassiliki
A1 Woest, Manon
A1 Kerstjens, Huib
A1 Sandham, David
A1 Gosens, Reinoud
A1 Kistemaker, Loes
YR 2020
UL http://erj.ersjournals.com/content/56/suppl_64/1418.abstract
AB 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.FootnotesCite this article as: European Respiratory Journal 2020; 56: Suppl. 64, 1418.This abstract was presented at the 2020 ERS International Congress, in session “Respiratory viruses in the "pre COVID-19" era”.This is an ERS International Congress abstract. No full-text version is available. Further material to accompany this abstract may be available at www.ers-education.org (ERS member access only).