IL-22/IL-22R1 signaling regulates the pathophysiology of chronic rhinosinusitis with nasal polyps via alteration of MUC1 expression

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• 作者：Yasuyuki Noyama^a ; Mitsuhiro Okano^a ; ^{mokano@cc.okayama-u.ac.jp} ; Tazuko Fujiwara^a ; Shin Kariya^a ; Takaya Higaki^a ; Takenori Haruna^a ; Sei-ichiro Makihara^b ; Kengo Kanai^c ; Takahisa Koyama^a ; Masami Taniguchi^d ; Jun-ichi Ishitoya^e ; Akira Kanda^f ; Yoshiki Kobayashi^f ; Mikiya Asako^f ; Koichi Tomoda^f ; Kazunori Nishizaki^a
• 关键词：Chronic rhinosinusitis with nasal polyps ; Exotoxins ; IL-22 ; MUC1 ; Staphylococcus aureus
• 刊名：Allergology International
• 出版年：2017
• 出版时间：January 2017
• 年：2017
• 卷：66
• 期：1
• 页码：42-51
• 全文大小：1650 K
• 卷排序：66

文摘

IL-22 is an IL-10-family cytokine that regulates chronic inflammation. We investigated the role of IL-22 and its receptor, IL-22R1, in the pathophysiology of chronic rhinosinusitis with nasal polyps (CRSwNP).MethodsIL-22 and IL-22R1 protein and mRNA expression in NP and in uncinate tissues (UT) from CRS and non-CRS patients was examined using immunohistochemistry and real-time PCR, respectively. Dispersed NP and UT cells were cultured with the Staphylococcus aureus exotoxins, staphylococcal enterotoxin B and alpha-toxin, following which exotoxin-induced IL-22 levels and their association with clinicopathological factors were analyzed. Effects of IL-22 on MUC1 expression and cytokine release in NP cells were also determined.ResultsIL-22 and IL-22R1 in NP were mainly expressed in infiltrating inflammatory cells and in epithelial cells, respectively. IL-22 mRNA levels in NP were significantly higher than those in UTs from non-CRS patients whereas IL-22R1 levels were conversely lower in NPs. NP cells produced substantial amounts of IL-22 in response to exotoxins. Exotoxin-induced IL-22 production by NP cells significantly and negatively correlated with the degree of local eosinophilia and postoperative computed tomography (CT) score, whereas conversely it positively correlated with the forced expiratory volume in 1s (FEV1)/forced vital capacity (FVC) ratio. IL-22 significantly enhanced MUC1 mRNA expression in NP cells. IL-22-induced MUC1 mRNA levels were significantly and positively correlated with IL-22R1 mRNA levels in NPs.ConclusionsThese data suggest that imbalance of IL-22/IL-22R1 signaling regulates the pathogenesis of CRSwNP, including local eosinophilia, via alteration of MUC1 expression.