The Anti-inflammation Role Of MMI-0100 In Ulcerative Colitis

Ulcerative Colitis(UC),a subtype of inflammatory bowel disease(IBD),which caused by a variety of factors.Complicated processes,both onset and development of IBD,in which genetic,immunologic factors,environmental aspect and enteric microorganism play important roles,then accelerate inflammatory.Inflammation related signaling pathways are phosphorylated activated in inflammatory state.Such as,p38 signal,by which activate the downstream MAPKAPK2(MK2)signal,and then biosynthesis of Tumor necrosis factor-?(TNF-?)are promoted,leading to more serious inflammation.Researchers found that Cell penetrating peptide MMI-0100 which contains 22 amino acids in its sequence is a inhibitor of KM2 signal and MMI-0100 can inhibit the process of activating of MK2 signal.Because of above reasons,we apply MMI-0100 in UC to detect whether MMI-0100 limit the development of inflammation by inhibiting MK2 signal.Mice drank 2% DSS solution for a week to form acute ulcerative colitis model in experiment,and then MMI-0100 was drunk with 1mg/kg at same time respectively.During this period,we monitored body weight,etc.characteristics of mice,and collected mice colon tissue after 7days.Then we observed the colon tissue damaged level and infiltration of inflammatory cells,and assessed the secretion of TNF-?,IL-6 ect.inflammatory cytokines in the colon orderly.Our work is infirm the anti-inflammation effect of MMI-0100 in 2% DSS-induced ulcerative colon mice.In addition,5-ASA was used with 5mg/kg as a control to compare effects of MMI-0100.RAW 264 and THP-1 cell are chosen to form LPS-induced cell inflammatory model with 1?g/mL LPS in vitro,but specially,THP-1 cell was induced after differentiation with 20ng/mL PMA condition for 72 h.Both RAW264 and THP-1 cell overexpression of proinflammatory cytokines after LPS-induced 24 h,and MMI-0100 present a anti-inflammatory role at 100 and 10 nM.In the following,we detected the expression of cytokines at mRNA and protein level respectively,to research anti-inflammatory in cell.According to experiments,MMI-0100 mitigates the weight loss and shorten of colon in ulcerative mice,inhibits the infiltration of inflammatory cells and TNF-?,IL-6 etc.secretion of inflammatory cytokines,restrains colon tissue damage caused by ulcerative colon inflammation.MMI-0100 inhibits the infiltration of inflammatory cells and secretion of TNF-?,IL-6 etc.cytokines in LPS-induced cell in addition.About the mechanism of MMI-0100 in inhibiting inflammatory,we detected the pMK2 signal,and we found that MMI-0100 can inhibit the synthesis and secretion of proinflammatory factor in DSS-induced UC mice and LPS-induced cell mode by inhibiting activation of MK2 signal.