Spinal cord injury(SCI)is one of the most devastating traumas,and the aberrant proliferation of astrocytes usually causes neurological deficits.However,the mechanism underlying astrocyte over-proliferation after SCI i...Spinal cord injury(SCI)is one of the most devastating traumas,and the aberrant proliferation of astrocytes usually causes neurological deficits.However,the mechanism underlying astrocyte over-proliferation after SCI is unclear.Grin2c(glutamate ionotropic receptor type 2c)plays an essential role in cell proliferation.Our bioinformatic analysis indicated that Grin2c and Ca^(2+)transport functions were inhibited in astrocytes after SCI.Suppression of Grin2c stimulated astrocyte proliferation by inhibiting the Ca^(2+)/calmodulin-dependent protein kinase 2b(CaMK2b)pathway in vitro.By screening different inflammatory factors,interleukin 1α(IL1α)was further found to inhibit Grin2c/Ca^(2+)/CaMK2b and enhance astrocyte proliferation in an oxidative damage model.Blockade of IL1αusing neutralizing antibody resulted in increased Grin2c expression and the inhibition of astrocyte proliferation post-SCI.Overall,this study suggests that IL1αpromotes astrocyte proliferation by suppressing the Grin2c/Ca^(2+)/CaMK2b pathway after SCI,revealing a novel pathological mechanism of astrocyte proliferation,and may provide potential targets for SCI repair.展开更多
白介素1受体辅助蛋白(IL1RAP)是白介素1 (IL-1)家族的共受体,通过与白介素1受体(IL-1R)结合形成多聚复合物并激活下游信号通路发挥生物学效应。IL1RAP介导的信号通路在各类恶性肿瘤中表现出促增殖和促侵袭、迁移的特性,包括血液系统肿...白介素1受体辅助蛋白(IL1RAP)是白介素1 (IL-1)家族的共受体,通过与白介素1受体(IL-1R)结合形成多聚复合物并激活下游信号通路发挥生物学效应。IL1RAP介导的信号通路在各类恶性肿瘤中表现出促增殖和促侵袭、迁移的特性,包括血液系统肿瘤、消化道肿瘤、乳腺癌、宫颈癌等。本综述旨在阐明IL1RAP介导的信号通路的生物学效应,以及IL1RAP在各类恶性肿瘤中作用机制的研究进展。Interleukin 1 receptor accessory protein (IL1RAP) is a co-receptor of the interleukin 1 (IL-1) family, which exerts biological effects by binding to the interleukin 1 receptor (IL-1R) to form a multimeric complex and activating the downstream signaling pathway. The signaling pathway mediated by IL1RAP shows pro-proliferative, pro-invasive, and migratory properties in various types of malignant tumors, including hematological tumors, gastrointestinal tract tumors, breast cancers, cervical cancer, etc. The aim of this review is to elucidate the biological effects of IL1RAP-mediated signaling pathway and the progress of the research on the mechanism of IL1RAP in various malignant tumors.展开更多
基金supported by the National Natural Science Foundation of China(82071362,82002899)the Basic Research Project of Shenzhen Science and Technology Innovation Commission(JCYJ202205303001577,JCYJ20190809165201646)Basic Research Projects of Shenzhen Science and Technology Program(JCYJ20180307150610733).
文摘Spinal cord injury(SCI)is one of the most devastating traumas,and the aberrant proliferation of astrocytes usually causes neurological deficits.However,the mechanism underlying astrocyte over-proliferation after SCI is unclear.Grin2c(glutamate ionotropic receptor type 2c)plays an essential role in cell proliferation.Our bioinformatic analysis indicated that Grin2c and Ca^(2+)transport functions were inhibited in astrocytes after SCI.Suppression of Grin2c stimulated astrocyte proliferation by inhibiting the Ca^(2+)/calmodulin-dependent protein kinase 2b(CaMK2b)pathway in vitro.By screening different inflammatory factors,interleukin 1α(IL1α)was further found to inhibit Grin2c/Ca^(2+)/CaMK2b and enhance astrocyte proliferation in an oxidative damage model.Blockade of IL1αusing neutralizing antibody resulted in increased Grin2c expression and the inhibition of astrocyte proliferation post-SCI.Overall,this study suggests that IL1αpromotes astrocyte proliferation by suppressing the Grin2c/Ca^(2+)/CaMK2b pathway after SCI,revealing a novel pathological mechanism of astrocyte proliferation,and may provide potential targets for SCI repair.
文摘白介素1受体辅助蛋白(IL1RAP)是白介素1 (IL-1)家族的共受体,通过与白介素1受体(IL-1R)结合形成多聚复合物并激活下游信号通路发挥生物学效应。IL1RAP介导的信号通路在各类恶性肿瘤中表现出促增殖和促侵袭、迁移的特性,包括血液系统肿瘤、消化道肿瘤、乳腺癌、宫颈癌等。本综述旨在阐明IL1RAP介导的信号通路的生物学效应,以及IL1RAP在各类恶性肿瘤中作用机制的研究进展。Interleukin 1 receptor accessory protein (IL1RAP) is a co-receptor of the interleukin 1 (IL-1) family, which exerts biological effects by binding to the interleukin 1 receptor (IL-1R) to form a multimeric complex and activating the downstream signaling pathway. The signaling pathway mediated by IL1RAP shows pro-proliferative, pro-invasive, and migratory properties in various types of malignant tumors, including hematological tumors, gastrointestinal tract tumors, breast cancers, cervical cancer, etc. The aim of this review is to elucidate the biological effects of IL1RAP-mediated signaling pathway and the progress of the research on the mechanism of IL1RAP in various malignant tumors.
文摘目的:制备针对白血病干细胞(LSC)表面标志蛋白IL1RAP(IL-1 receptor accessory protein)的特异性单克隆抗体并对其进行鉴定。方法:杂交瘤细胞3H6E10、10D8A7种植BALB/c小鼠腹腔,收获腹水,纯化后得到特异性抗人IL1RAP的单克隆抗体。分别应用非变性聚丙烯酰胺凝胶电泳(Nondenaturing-PAGE)、ELISA和Western blot法对纯化单克隆抗体分别进行抗体纯度、效价和敏感性检测。结果:获得了两种IL1RAP纯化单克隆抗体,命名为3H6E10 Mc Ab和10D8A7 Mc Ab,其纯度分别为95%和94%;两种纯化的单克隆抗体效价为1∶81000,且能特异性识别IL1RAP纯化蛋白、正常人及白血病病人的细胞内源性蛋白。结论:本研究成功制备了能特异性结合人IL1RAP的纯化单克隆抗体,为将来有效清除体内LSC提供了新途径。
