Inhibitors of MAPK Pathway ERK1/2 or p38 Prevent the IL-1β-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.

P38 MAPK Pharmacological Inhibitor SB203580 Alleviates Total Parenteral Nutrition-Induced Loss of Intestinal Barrier Function but Promotes Hepatocyte Lipoapoptosis

“…Thus, this phenomenon was attibuted to the possibility that the production of IL-1βwas, in part, due to p38 MAPK activation. Additionally, p38 MAPK pathway is essential to the IL-1β-mediated immune responses and loss of intestinal barrier function [41, 42]. In this study, we indicated that IL-1β could significantly increase the tight junction permeability in Caco-2 cells.…”

Mechanism of IL-1β Modulation of Intestinal Epithelial Barrier Involves p38 Kinase and Activating Transcription Factor-2 Activation

“…The p38 kinase pathway has been shown to play an important role in mediating some of the IL-1b-induced immune responses (34,35). The p38 kinase pathway is known to regulate wide-ranging proinflammatory responses, including stimulation of proinflammatory genes (36,37), induction of COX-2 (38), increases in iNOS expression (39), increases in adhesion molecule expression (40)(41)(42), and proliferation of inflammatory cells (43)(44)(45)(46).…”

Recombinant Human Plasminogen Activator Inhibitor-1 Promotes Cementogenic Differentiation of Human Periodontal Ligament Stem Cells

“…To confirm whether p38 and Smad2/3 play an essential role in rhPAI-1-induced cementogenic differentiation of hPDLSCs, we investigated the effects of their specific inhibitors, SB203580 and SIS3, respectively, on differentiation induction. 34,35 Compared to Alizarin red S staining positivity of rhPAI-1 group after 14 days of differentiation induction, decreased calcium nodule formation was observed in the presence of rhPAI-1 with the SB203580 and SIS3 group (Fig. 3C).…”