Role of NLRP3 Inflammasome on Different Phenotypes of Chronic Rhinosinusitis

Abstract

Background The pathophysiologic mechanisms of human chronic rhinosinusitis (CRS) are highly complex, and sinonasal colonization with pathogens is the first and most important step in this process. NLRP3, the main receptor activated by pathogen-associated molecular patterns (PAMPs), is associated with a variety of inflammatory diseases, including airway inflammation; however, the understanding of its role in CRS is limited. Objective By detecting the differential expression of the NLRP3 inflammasome and its downstream cytokines IL-1β and IL-18 between CRS patients and controls, between different CRS phenotypes (CRSsNP and CRSwNP), between mucosal tissue and polyp tissue, and further its relationship with neutrophilic/eosinic infiltration, we aimed to elucidate the biological role of the NLRP3 inflammasome in the pathophysiologic mechanisms of CRS. Methods Fifteen cases in each control, CRSsNP, and CRSwNP groups (subdivided into mucosa tissue and polyp tissue) were included in this study. Differential expression of NLRP3/caspase-1 and its downstream cytokines IL-1β and IL-18 was investigated, and its relationship with neutrophilic and eosinophilic infiltration was analyzed. Fluorescent immunohistochemistry (F-IHC) was used to assess NLRP3 and caspase-1 expression, RT-PCR was used for mRNA level quantitation, and western blotting was employed to analyze the protein concentrations. Results NLRP3 and cleaved caspase-1 were expressed at higher levels in both the CRSsNP and CRSwNP phenotypes than in the control nasal mucosa and at much higher levels in polyp tissue of CRSwNP ( P < .05), which was in line with the expression of cleaved IL-1β and cleaved IL-18 ( P < .05). Higher expression of NLRP3 had a mild correlation with neutrophilic infiltration but highly correlated with eosinophilic infiltration (R = 0.607, P < .01). Conclusions NLRP3 is involved in the pathogenesis of CRS, most likely by the NLRP3/caspase-1/IL-1β and IL-18 response. It induced eosinophilic infiltration in CRSwNP, especially in polyp tissue. As for whether NLRP3 induces neutrophilic infiltration, further experiments are needed to confirm.