Suppression of MUC5AC expression in human bronchial epithelial cells by interferon-γ

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• 作者：Takahito Oyanagi^a ; ^b ; Takumi Takizawa^a ; ^{takizawt@gunma-u.ac.jp} ; Akira Aizawa^a ; Orosoo Solongo^a ; Hisako Yagi^a ; Yutaka Nishida^a ; Harumi Koyama^a ; Akihiko Saitoh^b ; Hirokazu Arakawa^a
• 关键词：Bronchial epithelial cells ; Interferon-γ ; MUC5AC ; Mucin ; Sp1
• 刊名：Allergology International
• 出版年：2017
• 出版时间：January 2017
• 年：2017
• 卷：66
• 期：1
• 页码：75-82
• 全文大小：1176 K
• 卷排序：66

文摘

Excessive mucin secretion in the airway is an important feature of airway inflammatory diseases. MUC5AC expression is regulated by a variety of stimuli such as cytokines. Little is known about the role of interferon (IFN)-γ in MUC5AC expression in human bronchial epithelial cells.MethodsHuman pulmonary mucoepidermoid carcinoma cell line (NCI-H292) and normal human bronchial epithelial (NHBE) cells were used to assess the effects of IFN-γ on MUC5AC transcription.ResultsTransforming growth factor (TGF)-α and double-stranded RNA (polyI:C)-induced MUC5AC mRNA and protein expression was repressed by IFN-γ in a concentration-dependent manner. IFN-γ showed limited effects on TGF-α and polyI:C-induced activation of epidermal growth factor receptor (EGFR) and extracellular signal-regulated kinase (ERK). A chromatin immunoprecipitation assay indicated that Sp1 bound to its cognate sequence located on the MUC5AC promoter. The Sp1 inhibitor mithramycin A inhibited MUC5AC mRNA expression, implying a critical role for Sp1 in MUC5AC induction. Importantly, IFN-γ impeded Sp1 binding to the MUC5AC promoter.ConclusionsThese results suggest that IFN-γ represses MUC5AC expression, disturbing binding of Sp1 to its target sequences.