Bae Chang Hoon, Choi Yoon Seok, Na Hyung Gyun, Song Si-Youn, Kim Yong-Dae
From the 1 Department of Otorhinolaryngology-Head and Neck Surgery, College of Medicine, Yeungnam University, Daegu, Republic of Korea, and.
2 Regional Center for Respiratory Diseases, Yeungnam University Medical Center, Daegu, Republic of Korea.
Am J Rhinol Allergy. 2018 Mar;32(2):87-93. doi: 10.1177/1945892418762844. Epub 2018 Mar 23.
Mucin 5AC, oligomeric mucus/gel-forming (MUC5AC) expression is significantly increased in allergic and inflammatory airway diseases. Interleukin (IL) 36 gamma is predominantly expressed in airway epithelial cells and plays an important role in innate and adaptive immune responses. IL-36 gamma is induced by many inflammatory mediators, including cytokines and bacterial and viral infections. However, the association between IL-36 gamma and mucin secretion in human airway epithelial cells has not yet been fully investigated.
The objective of this study was to determine whether IL-36 gamma might play a role in the regulation of mucin secretion in airway epithelial cells. We investigated the effect and brief signaling pathway of IL-36 gamma on MUC5AC expression in human airway epithelial cells.
Enzyme immunoassay, immunoblot analysis, immunofluorescence staining, reverse transcriptase-polymerase chain reaction (PCR), and real-time PCR were performed in mucin-producing human airway epithelial NCI-H292 cells and in human nasal epithelial cells after pretreatment with IL-36 gamma, several specific inhibitors, or small interfering RNAs (siRNA).
IL-36 gamma induced MUC5AC expression and activated the phosphorylation of extracellular signal regulated kinase (ERK) 1 and 2, p38, and nuclear factor-kappa-light-chain-enhancer of activated B cells (NF-kappa B). IL-36 receptor antagonist significantly attenuated these effects. The specific inhibitor and siRNA of ERK1, ERK2, p38, and NF-kappa B significantly attenuated IL-36 gamma induced MUC5AC expression.
These results indicated that IL-36 gamma induced MUC5AC expression via the IL-36 receptor-mediated ERK1/2 and p38/NF-kappa B pathway in human airway epithelial cells.
黏蛋白5AC，即寡聚黏液/凝胶形成性（MUC5AC）在变应性和炎性气道疾病中表达显著增加。白细胞介素（IL）-36γ主要在气道上皮细胞中表达，在固有免疫和适应性免疫反应中起重要作用。IL-36γ由多种炎性介质诱导产生，包括细胞因子以及细菌和病毒感染。然而，IL-36γ与人类气道上皮细胞中黏蛋白分泌之间的关联尚未得到充分研究。
本研究的目的是确定IL-36γ是否可能在气道上皮细胞黏蛋白分泌的调节中发挥作用。我们研究了IL-36γ对人气道上皮细胞中MUC5AC表达的影响及简要信号通路。
在用IL-36γ、几种特异性抑制剂或小干扰RNA（siRNA）预处理后，对产生黏蛋白的人气道上皮NCI-H292细胞和人鼻上皮细胞进行酶免疫测定、免疫印迹分析、免疫荧光染色、逆转录聚合酶链反应（PCR）和实时PCR。
IL-36γ诱导MUC5AC表达，并激活细胞外信号调节激酶（ERK）1和2、p38以及活化B细胞核因子κB轻链增强子（NF-κB）的磷酸化。IL-36受体拮抗剂显著减弱了这些作用。ERK1、ERK2、p38和NF-κB的特异性抑制剂和siRNA显著减弱了IL-36γ诱导的MUC5AC表达。
这些结果表明，IL-36γ通过IL-36受体介导的ERK1/2和p38/NF-κB途径在人气道上皮细胞中诱导MUC5AC表达。
