Abbas Tavakoli https://orcid.org/0000-0003-2527-7017
Animals; Colitis (chemically induced, genetics); Colon; Cytokines; Dextran Sulfate (toxicity); Disease Models, Animal; Helicobacter; Humans; Indoles; Mice; Mice, Inbred C57BL; MicroRNAs (genetics)
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 (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.
We infected C57BL/6 mice with (), 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: 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. infection caused broad changes in mesenteric lymph node miRNA expression, but colitis-associated miRNAs were regulated similarly in infected and uninfected, DSS-treated mice. In spite of causing colitis exacerbation, infection did not prevent disease amelioration by I3C. I3C normalized both macrophage- and T cell-associated cytokines.
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.
Digital Object Identifier (DOI)
Published in World Journal of Gastroenterology, Volume 26, Issue 32, 2020, pages 4763-4785.
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Alkarkoushi, R., Hui, Y., Tavakoli, A., Singh, U., Nagarkatti, P., & Nagarkatti, M. et al. (2020). Immune and microRNA responses to Helicobacter muridarum infection and indole-3-carbinol during colitis. World Journal Of Gastroenterology, 26(32), 4763-4785. https://doi.org/10.3748/wjg.v26.i32.4763