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α-Melanocyte-stimulating hormone inhibits tumor necrosis factor α-stimulated MUC5AC expression in human nasal epithelial cells.

 Sang-Nam Lee  ;  Ji-Hwan Ryu  ;  Joo-Heon Yoon  ;  Kyu-Bo Kim  ;  Yoon-Ju Kim  ;  Hyun-Jae Lee  ;  Yeon-Ho Choi  ;  Jung-Hee Joo 
 American Journal of Respiratory Cell and Molecular Biology, Vol.44(5) : 716-724, 2011 
Journal Title
 American Journal of Respiratory Cell and Molecular Biology 
Issue Date
Mucin hypersecretion is an important clinical feature of several respiratory diseases, including asthma, cystic fibrosis, nasal allergy, rhinitis, and sinusitis. It has been shown that α-melanocyte-stimulating hormone (α-MSH), a proopiomelanocortin (POMC)-derived peptide, has immunomodulatory activities by inhibiting NF-κB activation induced by proinflammatory cytokines such as TNF-α. Because MUC5AC expression is known to be up-regulated by TNF-α via NF-κB activation, we evaluated the inhibitory effect of α-MSH on MUC5AC gene expression induced by TNF-α in normal human nasal epithelial (NHNE) cells. Melanocortin-1-receptor (MC-1R) was detected by RT-PCR, Western blotting, and immunofluorescent labeling in NHNE cells. α-MSH suppressed NF-κB/p65 phosphorylation induced by TNF-α as well as IkB-α degradation in a dose-dependent manner, as assessed by Western blotting. In addition, α-MSH inhibited TNF-α-induced nuclear translocation of NF-κB and NF-κB luciferase activity. Real-time quantitative PCR data showed that α-MSH inhibited TNF-α-induced expression of MUC5AC, and this effect of α-MSH was neutralized by knockdown of MC-1R using MC-1R shRNA lentivirus. Analyses using RT-PCR and Western blotting showed the expression of POMC and two key enzymes in the POMC processing, proprotein convertases (PC)1 and PC2, and 7B2, which is required for enzymatic activity of PC2, in normal human nasal mucosa. We conclude that α-MSH down-regulates MUC5AC expression by inhibiting TNF-α-induced NF-κB activity through MC-1R stimulation in NHNE cells and that normal human nasal mucosa possesses the POMC processing machinery. Therefore, α-MSH may be a promising candidate to decrease mucin overproduction initiated by NF-κB activation.
Appears in Collections:
1. Journal Papers (연구논문) > 5. Research Institutes (연구소) > Research Center for Human Natural Defense System (생체방어연구센터)
1. Journal Papers (연구논문) > 1. College of Medicine (의과대학) > Medical Research Center (임상의학연구센터)
1. Journal Papers (연구논문) > 1. College of Medicine (의과대학) > Yonsei Biomedical Research Center (연세의생명연구원)
1. Journal Papers (연구논문) > 1. College of Medicine (의과대학) > Dept. of Otorhinolaryngology (이비인후과학교실)
Yonsei Authors
김규보(Kim, Kyu Bo) ; 김윤주(Kim, Yoon Ju) ; 유지환(Ryu, Ji Hwan) ; 윤주헌(Yoon, Joo Heon) ; 이상남(Lee, Sang Nam) ; 이현재(Lee, Hyun Jae) ; 주정희(Joo, Jung Hee) ; 최연호(Choi, Yeon Ho)
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