Inhibitors of MAPK pathway ERK1/2 or p38 prevent the IL-1{beta}-induced up-regulation of SRP72 autoantigen in Jurkat cells.
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.
Arana-Argáez
Victor E
VE
From the Instituto de Investigación en Reumatología y del Sistema Músculo Esquelético, Guadalajara, Jalisco CP 44340.
Delgado-Rizo
Vidal
V
Laboratorio de Inmunología, Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara, Guadalajara, Jalisco CP 44340.
Pizano-Martínez
Oscar E
OE
Laboratorio de Inmunología, Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara, Guadalajara, Jalisco CP 44340.
Martínez-Garcia
Erika A
EA
From the Instituto de Investigación en Reumatología y del Sistema Músculo Esquelético, Guadalajara, Jalisco CP 44340.
Martín-Márquez
Beatriz T
BT
From the Instituto de Investigación en Reumatología y del Sistema Músculo Esquelético, Guadalajara, Jalisco CP 44340.
Muñoz-Gómez
Andrea
A
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.
Petri
Marcelo H
MH
From the Instituto de Investigación en Reumatología y del Sistema Músculo Esquelético, Guadalajara, Jalisco CP 44340.
Armendáriz-Borunda
Juan
J
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.
Espinosa-Ramírez
Guillermo
G
From the Instituto de Investigación en Reumatología y del Sistema Músculo Esquelético, Guadalajara, Jalisco CP 44340.
Zúñiga-Tamayo
Diego A
DA
From the Instituto de Investigación en Reumatología y del Sistema Músculo Esquelético, Guadalajara, Jalisco CP 44340.
Herrera-Esparza
Rafael
R
Universidad Autónoma de Zacatecas, Zacatecas, México CP 98000.
Vázquez-Del Mercado
Mónica
M
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.
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
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