TY - JOUR
T1 - IL-22/IL-22R1 signaling regulates the pathophysiology of chronic rhinosinusitis with nasal polyps via alteration of MUC1 expression
AU - Noyama, Yasuyuki
AU - Okano, Mitsuhiro
AU - Fujiwara, Tazuko
AU - Kariya, Shin
AU - Higaki, Takaya
AU - Haruna, Takenori
AU - Makihara, Sei ichiro
AU - Kanai, Kengo
AU - Koyama, Takahisa
AU - Taniguchi, Masami
AU - Ishitoya, Jun ichi
AU - Kanda, Akira
AU - Kobayashi, Yoshiki
AU - Asako, Mikiya
AU - Tomoda, Koichi
AU - Nishizaki, Kazunori
N1 - Funding Information:
The authors would like to thank Osamu Matsushita and Misato Hirai for discussions, Go Kuwayama for his assistance with immunohistochemistry, and Yuko Okano for her editorial assistance. This work was supported in part by grants from Ministry of Education, Culture, Sports, Science and Technology, Japan (23592511 and 25861652) and Ministry of Health, Labor and Welfare of Japan (H26-, H27-Research on measures for intractable disease-general-004).
Publisher Copyright:
© 2016 Japanese Society of Allergology
PY - 2017/1/1
Y1 - 2017/1/1
N2 - Background 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). Methods IL-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. Results IL-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. Conclusions These data suggest that imbalance of IL-22/IL-22R1 signaling regulates the pathogenesis of CRSwNP, including local eosinophilia, via alteration of MUC1 expression.
AB - Background 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). Methods IL-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. Results IL-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. Conclusions These data suggest that imbalance of IL-22/IL-22R1 signaling regulates the pathogenesis of CRSwNP, including local eosinophilia, via alteration of MUC1 expression.
KW - Chronic rhinosinusitis with nasal polyps
KW - Exotoxins
KW - IL-22
KW - MUC1
KW - Staphylococcus aureus
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U2 - 10.1016/j.alit.2016.04.017
DO - 10.1016/j.alit.2016.04.017
M3 - Article
C2 - 27502468
AN - SCOPUS:84994238897
SN - 1323-8930
VL - 66
SP - 42
EP - 51
JO - Allergology International
JF - Allergology International
IS - 1
ER -