Inflammasomes are important for maintaining intestinal homeostasis, and dysbiosis contributes to the pathology of inflammatory bowel disease （IBD） and increases the risk for colorectal cancer, Inflammasome defects c...Inflammasomes are important for maintaining intestinal homeostasis, and dysbiosis contributes to the pathology of inflammatory bowel disease （IBD） and increases the risk for colorectal cancer, Inflammasome defects contribute to chronic intestinal inflammation and increase the susceptibility to colitis in mice, However, the inflammasome sensor absent in melanoma 2 （AIM2） protects against coiorectal cancer in an inflammasome-independent manner through DNA-dependent protein kinase and Akt pathways, Yet, the roles of the AIM2 inflammasome in IBD and the early phases of colorectal cancer remain ill-defined, Here we show that the AIM2 inflammasome has a protective role in the intestine, During steady state, Aim2 deletion results in the loss of IL-18 secretion, suppression of the IL-22 binding protein （IL-22BP） in intestinal epithelial cells and consequent loss of the STAT3-dependent antimicrobial peptides （AMPs） Reg3β and Reg3γ, which promotes dysbiosis-linked colitis, During dextran sulfate sodium-induced colitis, a dysfunctional IL-18/IL-22BP pathway in Aim2^-/- mice promotes excessive IL-22 production and elevated STAT3 activation, Aim2^-/- mice further exhibit sustained STAT3 and Akt activation during the resolution of colitis fueled by enhanced Reg3b and Reg3g expression, This self-perpetuating mechanism promotes proliferation of intestinal crypt cells and likely contributes to the recently described increase in susceptibility of Aim2^-/- mice to colorectal cancer, Collectively, our results demonstrate a central role for the AIM2 inflammasome in preventing dysbiosis and intestinal inflammation through regulation of the IL-18/IL-22BP/IL-22 and STAT3 pathway and expression of select AMPs.展开更多
目的:探讨Reg3b在大鼠耳蜗中的分布情况及在噪声刺激前后的表达变化,为治疗噪声性聋提供新思路。方法:30只健康成年SD大鼠,分为噪声暴露组和正常对照组,利用110 dB SPL宽频稳态白噪声对噪声组进行噪声暴露,通过免疫组织荧光技术,观察Re...目的:探讨Reg3b在大鼠耳蜗中的分布情况及在噪声刺激前后的表达变化,为治疗噪声性聋提供新思路。方法:30只健康成年SD大鼠,分为噪声暴露组和正常对照组,利用110 dB SPL宽频稳态白噪声对噪声组进行噪声暴露,通过免疫组织荧光技术,观察Reg3b在正常及噪声刺激后成年SD大鼠耳蜗内的分布情况。采用实时定量PCR技术(Real time-PCR)方法检测大鼠接受噪声刺激前后Reg3b在耳蜗内的表达变化。结果:免疫组织荧光技术提示,Reg3b在噪声暴露后主要表达于大鼠耳蜗的内毛细胞、外毛细胞,以及螺旋神经节处,而正常大鼠耳蜗中Reg3b表达不明显或呈阴性表达。与噪声刺激前相比,噪声刺激后,Reg3b在mRNA水平表达较噪声前明显提高。结论:Reg3b在耳蜗内的分布及在噪声刺激后的表达显著升高提示其在噪声诱导的细胞死亡及对抗噪声损伤方面具有一定作用,可能成为治疗感音神经性聋的新靶点。展开更多
Subject Code:H10With the support by the National Natural Science Foundation of China,National Key Research and Development Program of China,and National Program for Support of Top-Notch Young Professionals,the researc...Subject Code:H10With the support by the National Natural Science Foundation of China,National Key Research and Development Program of China,and National Program for Support of Top-Notch Young Professionals,the research team led by Prof.Lai Yuping(赖玉平)at Shanghai Key Laboratory of Regulatory Biology,School of Life Sciences,East China Normal University,uncovered a critical role of regenerating islet-展开更多
文摘Inflammasomes are important for maintaining intestinal homeostasis, and dysbiosis contributes to the pathology of inflammatory bowel disease （IBD） and increases the risk for colorectal cancer, Inflammasome defects contribute to chronic intestinal inflammation and increase the susceptibility to colitis in mice, However, the inflammasome sensor absent in melanoma 2 （AIM2） protects against coiorectal cancer in an inflammasome-independent manner through DNA-dependent protein kinase and Akt pathways, Yet, the roles of the AIM2 inflammasome in IBD and the early phases of colorectal cancer remain ill-defined, Here we show that the AIM2 inflammasome has a protective role in the intestine, During steady state, Aim2 deletion results in the loss of IL-18 secretion, suppression of the IL-22 binding protein （IL-22BP） in intestinal epithelial cells and consequent loss of the STAT3-dependent antimicrobial peptides （AMPs） Reg3β and Reg3γ, which promotes dysbiosis-linked colitis, During dextran sulfate sodium-induced colitis, a dysfunctional IL-18/IL-22BP pathway in Aim2^-/- mice promotes excessive IL-22 production and elevated STAT3 activation, Aim2^-/- mice further exhibit sustained STAT3 and Akt activation during the resolution of colitis fueled by enhanced Reg3b and Reg3g expression, This self-perpetuating mechanism promotes proliferation of intestinal crypt cells and likely contributes to the recently described increase in susceptibility of Aim2^-/- mice to colorectal cancer, Collectively, our results demonstrate a central role for the AIM2 inflammasome in preventing dysbiosis and intestinal inflammation through regulation of the IL-18/IL-22BP/IL-22 and STAT3 pathway and expression of select AMPs.
文摘目的:探讨Reg3b在大鼠耳蜗中的分布情况及在噪声刺激前后的表达变化,为治疗噪声性聋提供新思路。方法:30只健康成年SD大鼠,分为噪声暴露组和正常对照组,利用110 dB SPL宽频稳态白噪声对噪声组进行噪声暴露,通过免疫组织荧光技术,观察Reg3b在正常及噪声刺激后成年SD大鼠耳蜗内的分布情况。采用实时定量PCR技术(Real time-PCR)方法检测大鼠接受噪声刺激前后Reg3b在耳蜗内的表达变化。结果:免疫组织荧光技术提示,Reg3b在噪声暴露后主要表达于大鼠耳蜗的内毛细胞、外毛细胞,以及螺旋神经节处,而正常大鼠耳蜗中Reg3b表达不明显或呈阴性表达。与噪声刺激前相比,噪声刺激后,Reg3b在mRNA水平表达较噪声前明显提高。结论:Reg3b在耳蜗内的分布及在噪声刺激后的表达显著升高提示其在噪声诱导的细胞死亡及对抗噪声损伤方面具有一定作用,可能成为治疗感音神经性聋的新靶点。
文摘Subject Code:H10With the support by the National Natural Science Foundation of China,National Key Research and Development Program of China,and National Program for Support of Top-Notch Young Professionals,the research team led by Prof.Lai Yuping(赖玉平)at Shanghai Key Laboratory of Regulatory Biology,School of Life Sciences,East China Normal University,uncovered a critical role of regenerating islet-
