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


METHODS
Human 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.


RESULTS
Transforming 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.


CONCLUSIONS
These results suggest that IFN-γ represses MUC5AC expression, disturbing binding of Sp1 to its target sequences.
Department of Pediatrics, Graduate School of Medicine, Gunma University, Gunma, Japan; Department of Pediatrics, Graduate School of Medicine, Niigata University, Niigata, Japan.
Takahito
T
Oyanagi
Department of Pediatrics, Graduate School of Medicine, Gunma University, Gunma, Japan. Electronic address: takizawt@gunma-u.ac.jp.
Takumi
T
Takizawa
Department of Pediatrics, Graduate School of Medicine, Gunma University, Gunma, Japan.
Akira
A
Aizawa
Department of Pediatrics, Graduate School of Medicine, Gunma University, Gunma, Japan.
Orosoo
O
Solongo
Department of Pediatrics, Graduate School of Medicine, Gunma University, Gunma, Japan.
Hisako
H
Yagi
Department of Pediatrics, Graduate School of Medicine, Gunma University, Gunma, Japan.
Yutaka
Y
Nishida
Department of Pediatrics, Graduate School of Medicine, Gunma University, Gunma, Japan.
Harumi
H
Koyama
Department of Pediatrics, Graduate School of Medicine, Niigata University, Niigata, Japan.
Akihiko
A
Saitoh
Department of Pediatrics, Graduate School of Medicine, Gunma University, Gunma, Japan.
Hirokazu
H
Arakawa
D001980:Bronchi / Q000166:cytology / Q000378:metabolism*; D045744:Cell Line, Tumor; D015536:Down-Regulation / Q000187:drug effects*; D004847:Epithelial Cells / Q000166:cytology / Q000378:metabolism*; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology*; D055271:Mucin 5AC / Q000096:biosynthesis*; D020545:Respiratory Mucosa / Q000166:cytology / Q000378:metabolism*; D020218:Response Elements; D016329:Sp1 Transcription Factor / Q000378:metabolism
C573415:IFNG protein, human; C524678:MUC5AC protein, human; D055271:Mucin 5AC; D016329:Sp1 Transcription Factor; C108209:SP1 protein, human; D007371:Interferon-gamma
Bronchial epithelial cells; Interferon-γ; MUC5AC; Mucin; Sp1