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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Autoantigens / biosynthesis*
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Autoantigens / immunology
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Dermatomyositis / drug therapy
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Dermatomyositis / immunology
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Dermatomyositis / metabolism
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Humans
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Immune Tolerance / drug effects
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Immune Tolerance / immunology
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Interleukin-1beta / immunology
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Interleukin-1beta / metabolism
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Interleukin-1beta / pharmacology*
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Jurkat Cells
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MAP Kinase Signaling System / drug effects*
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MAP Kinase Signaling System / immunology
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Mitogen-Activated Protein Kinase 1 / antagonists & inhibitors*
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Mitogen-Activated Protein Kinase 1 / immunology
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Mitogen-Activated Protein Kinase 1 / metabolism
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Mitogen-Activated Protein Kinase 3 / antagonists & inhibitors*
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Mitogen-Activated Protein Kinase 3 / immunology
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Mitogen-Activated Protein Kinase 3 / metabolism
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Protein Kinase Inhibitors / pharmacology*
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Protein Kinase Inhibitors / therapeutic use
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Rheumatic Diseases / drug therapy
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Rheumatic Diseases / immunology
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Rheumatic Diseases / metabolism
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Signal Recognition Particle / biosynthesis*
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Signal Recognition Particle / immunology
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Up-Regulation / drug effects*
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Up-Regulation / immunology
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p38 Mitogen-Activated Protein Kinases / antagonists & inhibitors*
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p38 Mitogen-Activated Protein Kinases / immunology
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p38 Mitogen-Activated Protein Kinases / metabolism
Substances
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Autoantigens
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IL1B protein, human
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Interleukin-1beta
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Protein Kinase Inhibitors
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SRP72 protein, human
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Signal Recognition Particle
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MAPK1 protein, human
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Mitogen-Activated Protein Kinase 1
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Mitogen-Activated Protein Kinase 3
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p38 Mitogen-Activated Protein Kinases