Immune and microRNA responses to Helicobacter muridarum infection and indole-3-carbinol during colitis  

作　　者：Rasha Raheem Alkarkoushi Yvonne Hui Abbas S Tavakoli Udai Singh Prakash Nagarkatti Mitzi Nagarkatti Ioulia Chatzistamou Marpe Bam Traci L Testerman 

机构地区：[1]Department of Pathology,Microbiology and Immunology,University of South Carolina School of Medicine,Columbia,SC 29209,United States [2]College of Nursing,University of South Carolina,University of South Carolina,Columbia,SC 29208,United States [3]Department of Medicine,Hematology and Oncology,University of Virginia School of Medicine,Charlottesville,VA 22908,United States

出　　处：《World Journal of Gastroenterology》2020年第32期4763-4785,共23页世界胃肠病学杂志（英文版）

基　　金：Supported by the National Institutes of Health,No.P20GM103641.

摘　　要：BACKGROUND Indole-3-carbinol(I3C)and other aryl hydrocarbon receptor agonists are known to modulate the immune system and ameliorate various inflammatory and autoimmune diseases in animal models,including colitis induced by dextran sulfate sodium(DSS).MicroRNAs(miRNAs)are also gaining traction as potential therapeutic agents or diagnostic elements.Enterohepatic Helicobacter(EHH)species are associated with an increased risk of inflammatory bowel disease,but little is known about how these species affect the immune system or response to treatment.AIM To determine whether infection with an EHH species alters the response to I3C and how the immune and miRNA responses of an EHH species compare with responses to DSS and inflammatory bowel disease.METHODS We infected C57BL/6 mice with Helicobacter muridarum(H.muridarum),with and without DSS and I3C treatment.Pathological responses were evaluated by histological examination,symptom scores,and cytokine responses.MiRNAs analysis was performed on mesenteric lymph nodes to further evaluate the regional immune response.RESULTS H.muridarum infection alone caused colonic inflammation and upregulated proinflammatory,macrophage-associated cytokines in the colon similar to changes seen in DSS-treated mice.Further upregulation occurred upon treatment with DSS.H.muridarum infection caused broad changes in mesenteric lymph node miRNA expression,but colitis-associated miRNAs were regulated similarly in H.muridarum-infected and uninfected,DSS-treated mice.In spite of causing colitis exacerbation,H.muridarum infection did not prevent disease amelioration by I3C.I3C normalized both macrophage-and T cell-associated cytokines.CONCLUSION Thus,I3C may be useful for inflammatory bowel disease patients regardless of EHH infection.The miRNA changes associated with I3C treatment are likely the result of,rather than the cause of immune response changes.

关 键 词：Helicobacter muridarum MICRORNA IMMUNE T regulatory cell T helper 17 cell COLITIS CYTOKINE 

分 类 号：R574.62[医药卫生—消化系统]