Immune and Microrna Responses To Infection and Indole-3-Carbinol During Colitis

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 (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 (), 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. 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

Immune and Microrna Responses To Infection and Indole-3-Carbinol During Colitis

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 (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 (), 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. 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

Helicobacter’s Effects on Colitis/Colon Cancer and the Response to Indole 3-Carbinol

Enterohepatic Helicobacter (EHH) species are gram-negative bacteria, which are poorly studied. Several studies suggest that EHH species contribute to inflammatory bowel disease IBD in humans. IBD and colorectal cancer (CRC) has emerged as a public health challenge worldwide. Indole-3-carbinol (I3C) is one of the natural dietary indoles abundant in Brassica (cruciferous) vegetables. The aryl hydrocarbon receptor (AhR) plays an essential role as a regulator by controlling the balance between Tregs and Th17 cells. The activation of AhR by ligands derived from food or intestinal microbiota is an essential control mechanism in that balance. Moreover, many studies showed indoles achieving chemo-preventive effects against cancer. We used the dextran sulfate sodium (DSS)-induced colitis mouse model to study the role of Helicobacter muridarum (Hm) bacteria with and without I3C treatment. We focused on the pathology outcomes after the bacterial infection and the I3C treatment during the DSS course. Weight loss, diarrhea, blood in the stool, and histopathology were measured. Inflammation markers were also measured in the plasma and the colon. We then studied the miRNA response. miRNAs are non-coding RNAs that can regulate genes involved in the immune responses. The purpose of the second study was to study the role of Helicobacter hepaticus (Hh). (Hh) can cause colitis in genetic or pharmacologically induced deficiencies of the Interleukin-10/Interleukin-10 receptor. We studied (Hh) infection role, in the DSS colitis model and AOM (Azoxymethane) /DSS colon cancer model in wild-type mice. Finally, the last study\u27s purpose was to examine the effects of different species of Helicobacter on developing acute gut injury in male and female mice with and without DSS treatment. The species used are known to infect humans: H. cinaedi, H. fennelliae, H. hepaticus, and H. pullorum. Similar pathology and immune response measurements were done for this study, as was done for the other studies