title: Inhibitors of MAPK pathway ERK1/2 or p38 prevent the IL-1{beta}-induced up-regulation of SRP72 autoantigen in Jurkat cells.
abstract: 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.
authors: From the Instituto de Investigación en Reumatología y del Sistema Músculo Esquelético, Guadalajara, Jalisco CP 44340.
authors: Victor E
authors: VE
authors: Arana-Argáez
authors: Laboratorio de Inmunología, Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara, Guadalajara, Jalisco CP 44340.
authors: Vidal
authors: V
authors: Delgado-Rizo
authors: Laboratorio de Inmunología, Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara, Guadalajara, Jalisco CP 44340.
authors: Oscar E
authors: OE
authors: Pizano-Martínez
authors: From the Instituto de Investigación en Reumatología y del Sistema Músculo Esquelético, Guadalajara, Jalisco CP 44340.
authors: Erika A
authors: EA
authors: Martínez-Garcia
authors: From the Instituto de Investigación en Reumatología y del Sistema Músculo Esquelético, Guadalajara, Jalisco CP 44340.
authors: Beatriz T
authors: BT
authors: Martín-Márquez
authors: From the Instituto de Investigación en Reumatología y del Sistema Músculo Esquelético, Guadalajara, Jalisco CP 44340; Pasante de Servicio Social en Medicina, Universidad Autónoma de Guadalajara, Guadalajara, Jalisco CP 45129.
authors: Andrea
authors: A
authors: Muñoz-Gómez
authors: From the Instituto de Investigación en Reumatología y del Sistema Músculo Esquelético, Guadalajara, Jalisco CP 44340.
authors: Marcelo H
authors: MH
authors: Petri
authors: Instituto de Biología Molecular en Medicina, Departamento de Biología Molecular y Genómica, Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara, Guadalajara, Jalisco CP 44340.
authors: Juan
authors: J
authors: Armendáriz-Borunda
authors: From the Instituto de Investigación en Reumatología y del Sistema Músculo Esquelético, Guadalajara, Jalisco CP 44340.
authors: Guillermo
authors: G
authors: Espinosa-Ramírez
authors: From the Instituto de Investigación en Reumatología y del Sistema Músculo Esquelético, Guadalajara, Jalisco CP 44340.
authors: Diego A
authors: DA
authors: Zúñiga-Tamayo
authors: Universidad Autónoma de Zacatecas, Zacatecas, México CP 98000.
authors: Rafael
authors: R
authors: Herrera-Esparza
authors: From the Instituto de Investigación en Reumatología y del Sistema Músculo Esquelético, Guadalajara, Jalisco CP 44340; División de Medicina Interna, Departamento de Reumatología, Hospital Civil "Dr. Juan I. Menchaca," Guadalajara, Jalisco CP 44340, México. Electronic address: dravme@hotmail.com.
authors: Mónica
authors: M
authors: Vázquez-Del Mercado
mesh_terms: D001324:Autoantigens / Q000096:biosynthesis* / Q000276:immunology; D003882:Dermatomyositis / Q000188:drug therapy / Q000276:immunology / Q000378:metabolism; D006801:Humans; D007108:Immune Tolerance / Q000187:drug effects / Q000276:immunology; D053583:Interleukin-1beta / Q000276:immunology / Q000378:metabolism / Q000494:pharmacology*; D019169:Jurkat Cells; D020935:MAP Kinase Signaling System / Q000187:drug effects* / Q000276:immunology; D019950:Mitogen-Activated Protein Kinase 1 / Q000037:antagonists & inhibitors* / Q000276:immunology / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000037:antagonists & inhibitors* / Q000276:immunology / Q000378:metabolism; D047428:Protein Kinase Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D012216:Rheumatic Diseases / Q000188:drug therapy / Q000276:immunology / Q000378:metabolism; D018271:Signal Recognition Particle / Q000096:biosynthesis* / Q000276:immunology; D015854:Up-Regulation / Q000187:drug effects* / Q000276:immunology; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors* / Q000276:immunology / Q000378:metabolism
chemical_list: D001324:Autoantigens; C508585:IL1B protein, human; D053583:Interleukin-1beta; D047428:Protein Kinase Inhibitors; C503636:SRP72 protein, human; D018271:Signal Recognition Particle; C535150:MAPK1 protein, human; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D048051:p38 Mitogen-Activated Protein Kinases