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c-Ets1 inhibits the interaction of NF-κB and CREB, and downregulates IL-1β-induced MUC5AC overproduction during airway inflammation.

 KS Song  ;  J-H Yoon  ;  KS Kim  ;  DW Ahn 
 MUCOSAL IMMUNOLOGY, Vol.5(2) : 207-215, 2012 
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Mucin hypersecretion is frequently observed in many inflammatory diseases of the human respiratory tract. As mucin hypersecretion refers to uncontrolled mucin expression and secretion during inflammation, studies examining the negative control mechanisms of mucin hypersecretion are vital in developing novel therapeutic medications. We hypothesized that the c-Ets1 induced by interleukin (IL)-1β would decrease MUC5AC overproduction by inhibiting the interaction of NF-κB with cAMP response element-binding protein (CREB) in vivo. Stimulation with IL-1β caused the direct binding of NF-κB and CREB to the MUC5AC promoter, thus increasing MUC5AC gene expression. However, IL-1β-induced MUC5AC messenger RNA levels were surprizingly downregulated by c-Ets1 (located -938 to -930). Interestingly, c-Ets1 also suppressed IL-1β-induced MUC5AC gene expression in vitro and in vivo by disrupting the interaction of NF-κB with CREB on the MUC5AC promoter. In addition, c-Ets1 also inhibited significant morphologic changes and inflammatory cell infiltration after IL-1β exposure in mouse lungs infected with either wild-type or shRNA-c-Ets1. Moreover, reactive oxygen species produced by NOX4 increased c-Ets1 gene expression and MUC5AC gene expression in alveolar macrophages from bronchoalveolar lavage fluid. These results suggest a molecular paradigm for the establishment of a novel mechanism underlying the negative regulation of mucin overproduction, thus enhancing our understanding of airway inflammation.
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1. College of Medicine (의과대학) > Dept. of Otorhinolaryngology (이비인후과학교실) > 1. Journal Papers
Yonsei Authors
Yoon, Joo Heon(윤주헌)
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