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MLN4924 protects against bleomycin-induced pulmonary fibrosis by inhibiting the early inflammatory process |pdf=|usr=}}{{28469786 }} gab.com Text MLN4924 protects against bleomycin-induced pulmonary fibrosis by inhibiting the early inflammatory process JO: Am J Transl Res http://www.kidney.de/pget.php?&tw=1&pmid=28469786 #FOAvip Pulmonary fibrosis is a complex pathological process characterized by massive destruction of the structure of lung tissues and aggravated pulmonary function impairment. The underlying mechanisms of pulmonary fibrosis are incompletely understood and therefore limited treatment options are available currently. Here, we report that MLN4924, an NEDD8 activation enzyme (NAE) activity-inhibiting molecule, blocks the maintenance and progression of established pulmonary fibrosis. We found that MLN4924 acts against bleomycin-induced pulmonary fibrosis mainly at the early inflammatory stage. Pharmacologically targeting the neddylation of Cullin-Ring E3 ligase (CRL) by MLN4924, significantly abrogated NF-?B responses, suppressed MAPK activity, and reduced secretion of TNF-?-elicited pro-inflammatory cytokines and MCP1-induced chemokines. MLN4924 inhibited pro-inflammatory responses while maintaining or increasing the production of the anti-inflammatory mediators such as anti-inflammatory interleukins (ILs) following bleomycin administration, which is closely correlated to its blocking NF-?B-mediated signaling. Consistently, our studies identified MLN4924 as a promising therapeutic drug for pulmonary fibrosis and suggested a potential role of MLN4924 that fine tunes the MAPK signaling pathway controlling the inflammatory reactions at the early stages of pulmonary fibrosis. In addition, our findings may broaden the potential practical application of MLN4924 as an effective therapeutic strategy against other inflammation-associated diseases. Twit Text FOAVip MLN4924 protects against bleomycin-induced pulmonary fibrosis by inhibiting the early inflammatory process ????Am J Transl Res http://www.kidney.de/pget.php?&tw=1&pmid=28469786 #FOAvip Twit Text # Free Paper on # # # # # LINK http://www.kidney.de/pget.php?&tw=1&pmid=28469786 #FOAvip English Wikipedia <ref>{{Cite pmid|28469786 }}</ref> MLN4924 protects against bleomycin-induced pulmonary fibrosis by inhibiting the early inflammatory process #MMPMID28469786 Deng Q ; Zhang J ; Gao Y ; She X ; Wang Y ; Wang Y ; Ge X Am J Transl Res 2017[]; 9 (4 ): 1810-1821 PMID28469786 show ga Pulmonary fibrosis is a complex pathological process characterized by massive destruction of the structure of lung tissues and aggravated pulmonary function impairment. The underlying mechanisms of pulmonary fibrosis are incompletely understood and therefore limited treatment options are available currently. Here, we report that MLN4924, an NEDD8 activation enzyme (NAE) activity-inhibiting molecule, blocks the maintenance and progression of established pulmonary fibrosis. We found that MLN4924 acts against bleomycin-induced pulmonary fibrosis mainly at the early inflammatory stage. Pharmacologically targeting the neddylation of Cullin-Ring E3 ligase (CRL) by MLN4924, significantly abrogated NF-?B responses, suppressed MAPK activity, and reduced secretion of TNF-?-elicited pro-inflammatory cytokines and MCP1-induced chemokines. MLN4924 inhibited pro-inflammatory responses while maintaining or increasing the production of the anti-inflammatory mediators such as anti-inflammatory interleukins (ILs) following bleomycin administration, which is closely correlated to its blocking NF-?B-mediated signaling. Consistently, our studies identified MLN4924 as a promising therapeutic drug for pulmonary fibrosis and suggested a potential role of MLN4924 that fine tunes the MAPK signaling pathway controlling the inflammatory reactions at the early stages of pulmonary fibrosis. In addition, our findings may broaden the potential practical application of MLN4924 as an effective therapeutic strategy against other inflammation-associated diseases. äMLN4924 protects against bleomycin-induced pulmonary fibrosis by inhib(epmc).pdf DeepDyve Pubget Overpricing