Interleukin -19 Up-Regulates Mucin 5AC Production in Patients with Chronic Rhinosinusitis via STAT3 Pathway

Abstract

Background: The mucin gene MUC5AC is highly expressed both in chronic respiratory inflammatory diseases and in inflammatory bowel disease where mucin secretion is regulated by members of the interleukin IL-20 subfamily. This study was conducted to determine the roles and mechanisms of IL-19, a member of the IL-20 subfamily, in regulating MUC5AC production in chronic rhinosinusitis (CRS). Methods: We analyzed the expression of mucin and MUC5AC in the nasal mucosa of patients with CRS by periodic acid Schiff (PAS) staining and immunohistochemical examination. Real-time quantitative PCR, ELISA, confocal microscopy and western blotting were used to measure MUC5AC expression in primary human nasal epithelium cells (PHNECs) stimulated with recombinant human IL-19 (rhIL-19), IL-19 receptor siRNA transfection or control. The involvement of the STAT3 signaling pathways was examined by the use of cryptotanshinone (CRY, an inhibitor of signal transducer and activator of transcription [STAT]3). Findings: Mucin and MUC5AC were significantly increased in mucosa of CRS with nasal polyps (CRSwNP) and CRS without nasal polyps (CRSsNP) compared to mucosa isolated from control who had no CRS, but there were no significant differences between these two groups. Pretreatment with rhIL-19 up-regulated the expression of MUC5AC in both mRNA and protein levels in PHNECs. Knockdown of IL-20R2 and pretreatment with CRY attenuated MUC5AC production induced by rhIL-19. Interpretation: We propose that mucin, MUC5AC and IL-19 are highly expressed in CRS and IL-19 up-regulates MUC5AC-induced mucin production via the STAT3 pathway, highlighting the important role IL-19 may play in mucin production in chronic respiratory diseases. Funding Statement: TThis study was supported by grants from the National Natural Science Foundation of China (No. 81371073, No. 81670913, No. 81500769, No. 81671611) and the Guangdong Introducing Innovative and Entrepreneurial Teams (2016ZT06S252). Declaration of Interests: The authors have no conflicts of interest to declare. Ethics Approval Statement: The protocol was approved by the ethics committee for clinical medical research at Third Affiliated Hospital of Sun Yat-sen University (No∙ [2016]2-26). All enrolled subjects had been given their written informed consent.