Tianyong Hu1, Wenhui Hu2, Li Ma1, Xianhai Zeng1, Jiangqi Liu1, Baohui Cheng1, Pingchang Yang3, Shuqi Qiu1, Gui Yang1, Donghui Chen4, Zhiqiang Liu5. 1. Longgang ENT Hospital, Institute of ENT and Shenzhen Key Laboratory of ENT, Shenzhen, China. 2. Zunyi Medical College, Zunyi, China. 3. Shenzhen University School of Medicine and State Key Laboratory of Respiratory Disease for Allergy at Shenzhen University, Shenzhen, China. 4. Children's Hospital Affiliated to Zhengzhou University, Zhengzhou, China. Electronic address: chendh0708@126.com. 5. Longgang ENT Hospital, Institute of ENT and Shenzhen Key Laboratory of ENT, Shenzhen, China. Electronic address: liuzhiqiang05312438@126.com.
Abstract
AIM: To investigate whether the intrarectal administration of the ubiquitin E3 ligase A20 (A20) attenuates intestinal inflammation and influences regulatory T cells in experimental colitis. METHODS: A dextran sulfate sodium induced chronic colitis mouse model was established. The symptoms and manifestations of colitis and the severity of colonic mucosal inflammation were evaluated. The protective role of A20 expression in the intestine was analyzed after the administration of a pVAX1-A20 recombinant eukaryotic vector, which was encapsulated into poly(L-lactide-co-glycolide) as a nanoparticle. RESULTS: pVAX1-A20 administration markedly ameliorated colonic tissue damage and reduced intestinal inflammation via the suppression of the mucosal mitogen-activated protein kinase and nuclear factor (NF)-κB signaling cascade. Furthermore, pVAX1-A20 promoted the splenic regulatory T cell population and forkhead box P3 expression in colonic tissue. CONCLUSION: A20 plays a key role in the regulation of intestinal inflammation and that the overexpression of A20 in the intestine protects mice from dextran sulfate sodium induced chronic colitis.
AIM: To investigate whether the intrarectal administration of the ubiquitin E3 ligase A20 (A20) attenuates intestinal inflammation and influences regulatory T cells in experimental colitis. METHODS: A dextran sulfate sodium induced chronic colitismouse model was established. The symptoms and manifestations of colitis and the severity of colonic mucosal inflammation were evaluated. The protective role of A20 expression in the intestine was analyzed after the administration of a pVAX1-A20 recombinant eukaryotic vector, which was encapsulated into poly(L-lactide-co-glycolide) as a nanoparticle. RESULTS: pVAX1-A20 administration markedly ameliorated colonic tissue damage and reduced intestinal inflammation via the suppression of the mucosal mitogen-activated protein kinase and nuclear factor (NF)-κB signaling cascade. Furthermore, pVAX1-A20 promoted the splenic regulatory T cell population and forkhead box P3 expression in colonic tissue. CONCLUSION:A20 plays a key role in the regulation of intestinal inflammation and that the overexpression of A20 in the intestine protects mice from dextran sulfate sodium induced chronic colitis.
Authors: Michael J Mitchell; Margaret M Billingsley; Rebecca M Haley; Marissa E Wechsler; Nicholas A Peppas; Robert Langer Journal: Nat Rev Drug Discov Date: 2020-12-04 Impact factor: 84.694