INTRODUCTION: Chronic rhinosinusitis with nasal polyps (CRSwNP) is an inflammatory disorder of the sinonasal mucosa that is frequently associated with microbial colonization. Innate defense mechanisms at the mucosal surface are critical in protecting the host from airborne environmental pathogens. Recent studies of skin and gastrointestinal tract inflammatory diseases have shown that stimulation of the interleukin-22 receptor (IL-22R1) nonspecifically increases innate immune responses. The potential role of IL-22R1 in the pathogenesis of CRSwNP has never been explored. STUDY DESIGN: Prospective. METHODS: Nine controls and 19 subjects with CRS were prospectively enrolled prior to undergoing endoscopic sinus surgery. Nasal epithelial cells were cultured from surgically obtained ethmoid mucosa and IL-22R1 protein expression was examined via flow cytometry. RNA was extracted from whole mucosal samples and real-time polymerase chain reaction (PCR) was employed to determine expression of IL22 and IL-22R1. Subjects were followed for at least 6 months postoperative to assess for recurrence or persistence of polyps. RESULTS: Flow cytometry demonstrated the expression of IL-22R1 protein on the surface of cultured nasal epithelial cells. IL-22R1 mRNA was expressed in 100% of the controls and CRSsNP. However, IL-22R1 was only expressed in 55% of patients with recalcitrant CRSwNP. Additionally, levels of IL22R1 were significantly lower in recalcitrant CRSwNP compared to controls and CRSsNP. IL22 levels did not reach statistical significance. CONCLUSIONS: In this study, we demonstrate IL-22R1 mRNA and protein expression on nasal epithelial cells. Failure of medical and surgical therapy in CRSwNP is associated with significantly decreased expression of IL-22R1. Further research is needed to determine the potential of IL-22R1 as a therapeutic target in CRSwNP.
INTRODUCTION:Chronic rhinosinusitis with nasal polyps (CRSwNP) is an inflammatory disorder of the sinonasal mucosa that is frequently associated with microbial colonization. Innate defense mechanisms at the mucosal surface are critical in protecting the host from airborne environmental pathogens. Recent studies of skin and gastrointestinal tract inflammatory diseases have shown that stimulation of the interleukin-22 receptor (IL-22R1) nonspecifically increases innate immune responses. The potential role of IL-22R1 in the pathogenesis of CRSwNP has never been explored. STUDY DESIGN: Prospective. METHODS: Nine controls and 19 subjects with CRS were prospectively enrolled prior to undergoing endoscopic sinus surgery. Nasal epithelial cells were cultured from surgically obtained ethmoid mucosa and IL-22R1 protein expression was examined via flow cytometry. RNA was extracted from whole mucosal samples and real-time polymerase chain reaction (PCR) was employed to determine expression of IL22 and IL-22R1. Subjects were followed for at least 6 months postoperative to assess for recurrence or persistence of polyps. RESULTS: Flow cytometry demonstrated the expression of IL-22R1 protein on the surface of cultured nasal epithelial cells. IL-22R1 mRNA was expressed in 100% of the controls and CRSsNP. However, IL-22R1 was only expressed in 55% of patients with recalcitrant CRSwNP. Additionally, levels of IL22R1 were significantly lower in recalcitrant CRSwNP compared to controls and CRSsNP. IL22 levels did not reach statistical significance. CONCLUSIONS: In this study, we demonstrate IL-22R1 mRNA and protein expression on nasal epithelial cells. Failure of medical and surgical therapy in CRSwNP is associated with significantly decreased expression of IL-22R1. Further research is needed to determine the potential of IL-22R1 as a therapeutic target in CRSwNP.
Authors: Robert C Kern; David B Conley; William Walsh; Rakesh Chandra; Atsushi Kato; Anju Tripathi-Peters; Leslie C Grammer; Robert P Schleimer Journal: Am J Rhinol Date: 2008-09-10