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 indu...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.展开更多
【目的】初步探讨与单纯疱疹病毒糖蛋白D竞争结合疱疹病毒侵入介体的淋巴毒素类似物(lymphotoxin-like inducible protein that competes with glycoprotein D for herpesvirus entry on T cells,LIGHT)在抗衣原体感染免疫及介导衣原体...【目的】初步探讨与单纯疱疹病毒糖蛋白D竞争结合疱疹病毒侵入介体的淋巴毒素类似物(lymphotoxin-like inducible protein that competes with glycoprotein D for herpesvirus entry on T cells,LIGHT)在抗衣原体感染免疫及介导衣原体生殖道病理损伤过程的作用。【方法】用1×104IFUs的Mo Pn经生殖道感染野生型(wild type,wt)、LIGHT KO小鼠,每组一半小鼠于感染后49d,再次感染相同剂量的Mo Pn。每隔3-4 d取生殖道分泌物,测定其中衣原体包涵体的数量。初次感染后80d,处死小鼠,眼眶取血,分离血清,用间接免疫荧光法测定其中抗体类型及效价;同时分离生殖道,肉眼观察其输卵管、子宫角水肿程度,然后甲醛固定、切片,H&E染色后,显微镜下观察各组织炎性浸润程度和管腔水肿程度。分离小鼠脾细胞,体外用衣原体EB刺激,测定上清中IL-4、IL-5、IL-17和IFN-γ等细胞因子水平。【结果】LIGHT KO小鼠阴道带菌时间与wt组相当,大部分小鼠均在原发感染后28d左右完全清除感染,且均产生对再次感染的免疫力。LIGHT KO和wt小鼠子宫角和输卵管均出现一定程度的病变,但差异无统计学意义。两组小鼠在原发和继发感染Mo Pn后,均产生高效价的特异性抗Mo Pn Ig G抗体,总抗体及各Ig G抗体亚类效价差异均无统计学意义(P>0.05),且Ig G2a/Ig G1比值均大于1。和wt小鼠一样,LIGHT KO小鼠脾淋巴细胞经衣原体再次刺激后均可产生较高水平的IFN-γ和IL-17,且未能检测到IL-4和IL-5。【结论】小鼠抗Mo Pn生殖道感染及Mo Pn引起的生殖道病理损伤不依赖于LIGHT信号通路。展开更多
基金Supported by the National Institutes of Health,No.P20GM103641.
文摘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.
文摘【目的】初步探讨与单纯疱疹病毒糖蛋白D竞争结合疱疹病毒侵入介体的淋巴毒素类似物(lymphotoxin-like inducible protein that competes with glycoprotein D for herpesvirus entry on T cells,LIGHT)在抗衣原体感染免疫及介导衣原体生殖道病理损伤过程的作用。【方法】用1×104IFUs的Mo Pn经生殖道感染野生型(wild type,wt)、LIGHT KO小鼠,每组一半小鼠于感染后49d,再次感染相同剂量的Mo Pn。每隔3-4 d取生殖道分泌物,测定其中衣原体包涵体的数量。初次感染后80d,处死小鼠,眼眶取血,分离血清,用间接免疫荧光法测定其中抗体类型及效价;同时分离生殖道,肉眼观察其输卵管、子宫角水肿程度,然后甲醛固定、切片,H&E染色后,显微镜下观察各组织炎性浸润程度和管腔水肿程度。分离小鼠脾细胞,体外用衣原体EB刺激,测定上清中IL-4、IL-5、IL-17和IFN-γ等细胞因子水平。【结果】LIGHT KO小鼠阴道带菌时间与wt组相当,大部分小鼠均在原发感染后28d左右完全清除感染,且均产生对再次感染的免疫力。LIGHT KO和wt小鼠子宫角和输卵管均出现一定程度的病变,但差异无统计学意义。两组小鼠在原发和继发感染Mo Pn后,均产生高效价的特异性抗Mo Pn Ig G抗体,总抗体及各Ig G抗体亚类效价差异均无统计学意义(P>0.05),且Ig G2a/Ig G1比值均大于1。和wt小鼠一样,LIGHT KO小鼠脾淋巴细胞经衣原体再次刺激后均可产生较高水平的IFN-γ和IL-17,且未能检测到IL-4和IL-5。【结论】小鼠抗Mo Pn生殖道感染及Mo Pn引起的生殖道病理损伤不依赖于LIGHT信号通路。
