Expression of cysteinyl leukotriene receptor GPR17 in eosinophilic and non-eosinophilic chronic rhinosinusitis with nasal polyps.

Abstract

The cysteinyl leukotrienes (cysLTs) are proinflammatory lipid mediators that act on the type 1 cysLT receptor (CysLT1R) in the pathogenesis of chronic rhinosinusitis with nasal polyps (CRSwNP). GPR17, a G protein-coupled orphan receptor with homology to the cysLT receptors, has been proposed as a damage sensor during inflammation. However, the expression and correlation of GPR17 and CysLT1R in eosinophilic CRSwNP (ECRS) and non-eosinophilic CRSwNP (non-ECRS) have not been well investigated. To evaluate the expression of GPR17 and its correlation with CysLT1R in the 2 CRSwNP subsets. Polyp tissues were collected from CRSwNP subjects (15 ECRS and 14 non-ECRS), and uncinate processes were collected from 12 CRSsNP subjects and 13 control subjects. The mRNA and protein levels of GPR17 and CysLT1R were examined using qRT-PCR, immunohistochemistry, and western blotting. Additionally, the correlation between GPR17 and CysLT1R at the mRNA and protein levels was evaluated. All assays were performed in a blinded manner. Polyp tissues exhibited significantly increased GPR17 expression relative to uncinate process tissues from CRSsNP patients, or healthy controls (P=0.0012 and P<0.0001, respectively). Compared with the non-ECRS subset, the ECRS subset showed significantly increased GPR17 expression. Moreover, the GPR17 expression was positively correlated with CysLT1R in nasal polyps. The increased expression of GPR17 in nasal polyps and the differential expression between eosinophilic and non-eosinophilic CRSwNP subsets suggest that these subsets may have distinct pathogenic mechanisms. The positive correlation between GPR17 and CysLT1R in polyp tissues might imply substantial regulatory mechanisms that must be elucidated.