Abstract
Activation of the DP2/CRTh2 receptor by prostaglandin D2 (PGD2) in the airway mediates pro-inflammatory responses from immune cells and epithelial remodelling. The airway smooth muscle (ASM) is dysfunctional in asthma with an increase in mass and infiltration by mast cells which release PGD2 following allergen challenge. The role of the PGD2/CRTh2 axis in ASM in asthma has not been studied extensively.
Expression and function of CRTh2 in primary ASM cells from asthmatics was assessed by flow cytometry, migration in a wound healing assay, F-actin content by phalloidin fluorescence, α-SMA expression and cell size/granularity by flow cytometry. PGD2 synthase (PGDS) expression was assessed by gene array.
ASM cells expressed cell surface CRTh2 (CRTH2/isotype control geometric mean fluorescence intensity (gMFI): 1.4±0.1, p<0.001, n=13) and significant amounts of L-PGDS mRNA (8.0±2.4% β-actin mRNA, n=6). CRTh2 activation by endogenous PGD2 was inhibited by the CRTh2 specific antagonist CAY10471 for 24 h, which resulted in reduced ASM migration and F-actin content but had no effect on α-SMA expression or cell size/granularity (Table 1).
The CRTh2 antagonist CAY10471 reduces ASM migration and F-actin content. ASM-derived PGD2 may play a role in promoting ASM migration and could contribute to increased ASM mass in asthma.
- Copyright ©the authors 2016
