Inhibitors of MAPK pathway ERK1/2 or p38 prevent the IL-1{beta}-induced up-regulation of SRP72 autoantigen in Jurkat cells.
Inhibitors of MAPK pathway ERK1/2 or p38 prevent the IL-1{beta}-induced up-regulation of SRP72 autoantigen in Jurkat cells.
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DOI：
10.1074/jbc.m110.121087
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发表时间：
2010-10-22
期刊：
影响因子：
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通讯作者：
Vázquez-Del Mercado M
中科院分区：
文献类型：
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作者：
Arana-Argáez VE;Delgado-Rizo V;Pizano-Martínez OE;Martínez-Garcia EA;Martín-Márquez BT;Muñoz-Gómez A;Petri MH;Armendáriz-Borunda J;Espinosa-Ramírez G;Zúñiga-Tamayo DA;Herrera-Esparza R;Vázquez-Del Mercado M
磷酸化是细胞水平上最重要的翻译后事件，受蛋白激酶调节。MAPK在重要的细胞信号通路中起着关键作用。据推测，磷酸化可能在诱导对某些自身抗原（如SRP72）的断裂耐受性中起作用。本研究的目的是利用MAPK抑制剂存在的重组人（rh）IL-1β刺激Jurkat细胞的体外模型，探索SRP72多肽的磷酸化和过表达途径。我们使用Jurkat细胞作为底物，在不同浓度的MAPK抑制剂存在下，用rhIL-1β刺激Jurkat细胞，通过免疫沉淀、免疫沉淀- western blotting和实时PCR进行体外时间过程实验。我们的研究结果表明，rhIL-1β导致Jurkat细胞中SRP72蛋白表达上调和磷酸化。MAPK通路ERK1/2或p38α/β抑制剂下调SRP72自身抗原在rhIL-1β刺激的Jurkat细胞中的表达。我们的结果强调了研究自身抗原的激活和过表达途径的重要性。有必要对各种激酶途径进行仔细的研究，包括皮肌炎和其他风湿性疾病中的MAPK，以帮助解释自身抗原的激活和抑制途径。对这一过程的理解可能有助于开发新的疗法来预防和控制对自身正常蛋白质的耐受性丧失。
Phosphorylation is the most important post-translational event at a cellular level that is regulated by protein kinases. MAPK is a key player in the important cellular signaling pathway. It has been hypothesized that phosphorylation might have a role in the induction of break tolerance against some autoantigens such as SRP72. The aim of this study was to explore the pathways of phosphorylation and overexpression of the SRP72 polypeptide, using an in vitro model of Jurkat cells stimulated by recombinant human (rh)IL-1β in the presence of MAPK inhibitors. We used Jurkat cells as a substrate stimulated with rhIL-1β in the presence of MAPK inhibitors at different concentrations in a time course in vitro experiment by immunoprecipitation, immunoprecipitation-Western blotting, and real time PCR. Our results showed that rhIL-1β causes up-regulation of protein expression and phosphorylation of SRP72 in Jurkat cells. Inhibitors of the MAPK pathway ERK1/2 or p38α/β down-regulate the expression of SRP72 autoantigen in Jurkat cells stimulated by rhIL-1β. Our results highlight the importance of studying the pathways of activation and overexpression of autoantigens. It will be necessary to perform careful research on various kinases pathways, including MAPK in dermatomyositis and other rheumatic diseases, to help to explain the routes of activation and inhibition of autoantigens. The understanding of this process may help to develop new therapies to prevent and control the loss of tolerance toward own normal proteins.