Kinin Upregulates CXCL1 and CXCL8 Chemokine Expression in Human Nasal Mucosa–Derived Fibroblasts

Abstract

Objectives: Chronic rhinosinusitis (CRS) is a chronic inflammatory disease involving the mucosa of the nasal cavity and sinuses. It can be classified into CRS with nasal polyps (CRSwNP) and without nasal polyps (CRSsNP). It is often described as a chronic inflammatory condition of the sinonasal mucosa and followed by a continuous tissue remodeling process. The CXC chemokine such as CXCL1 and CXCL8 are primarily chemotactic for endothelial cells and neutrophils, whch are potent promoters of angiogensis and inflammation. Methods: In this study, we examined the effects of kinin on CXC chemokine expression in human nasal fibroblasts from mucosa specimens of patients with CRSsNP. Results: We found kinin increased CXCL1 and CXCL8 release in a concentration- and time-dependent manner, as determined by enzyme-linked immunosorbent assay. In parallel, reverse transcriptase polymerase chain reaction analysis showed the kinin increased CXCL1 and CXCL8 mRNA level, suggesting this process involved transcriptional regulation. The increased CXCL chemokines appeared to have chemoattractive ability toward monocyte. We found monocyte migration increased as monocytes and fibroblasts were cocultured and the fibroblasts were stimulated with kinin in an indirect transwell co-culture system. Conclusions: Our results suggest that kinin may play a role in causing chemokine release and recruit leukocytes infiltration in the nasal inflammation microenvironment during chronic rhinosinusitis.