Characterization of protein tyrosine phosphatase H1 knockout mice in animal models of local and systemic inflammation

Abstract

BackgroundPTPH1 is a protein tyrosine phosphatase expressed in T cells but its effect on immune response is still controversial. PTPH1 dephosphorylates TCRzeta in vitro, inhibiting the downstream inflammatory signaling pathway, however no immunological phenotype has been detected in primary T cells derived from PTPH1-KO mice. The aim of the present study is to characterize PTPH1 phenotype in two in vivo inflammatory models and to give insights in possible PTPH1 functions in cytokine release.MethodsWe challenged PTPH1-KO mice with two potent immunomodulatory molecules, carrageenan and LPS, in order to determine PTPH1 possible role in inflammatory response in vivo. Cytokine release, inflammatory pain and gene expression were investigated in challenged PTPH1-WT and KO mice.ResultsThe present study shows that carrageenan induces a trend of slightly increased spontaneous pain sensitivity in PTPH1-KO mice compared to WT (wild-type) littermates, but no differences in cytokine release, induced pain perception and cellular infiltration have been detected between the two genotypes in this mouse model. On the other hand, LPS-induced TNFα, MCP-1 and IL10 release was significantly reduced in PTPH1-KO plasma compared to WTs 30 and 60 minutes post challenge. No cytokine release modulation was detectable 180 minutes post LPS challenge.ConclusionIn conclusion, the present study points out a slight potential role for PTPH1 in spontaneous pain sensitivity and it indicates that this phosphatase might play a role in the positive regulation of the LPS-induced cytokines release in vivo, in contrast to previous reports indicating PTPH1 as potential negative regulator of immune response.

Hereditable variants of classical protein tyrosine phosphatase genes: Will they prove innocent or guilty?

“…PTPH1 is rather broadly expressed, whereas highest PTP-MEG1 levels are found in brain and in cells of the immune system. Although in vitro studies pointed to a regulatory role for these phosphatases in the immune response, notably in T-cell receptor signaling, this was not apparent in mouse knockout studies (Bauler et al, 2008;Patrignani et al, 2010). Additionally, PTP-MEG1 knockouts displayed behavioral abnormalities (Kina et al, 2007).…”

Beyond the Cell Surface: Targeting Intracellular Negative Regulators to Enhance T cell Anti-Tumor Activity

“…However, PTPH1 knockdown mice did not show significant differences in TCR-activation or cytokine production. Further, lipopolysaccharide (LPS)-challenged PTPH1 knockdown mice showed a decrease in MCP-1 and IL10 release indicating that PTPH1 might be dispensable for T cell activation [188,189]. The potential for PTPH1 as a target for immunotherapies has not, to date, been addressed.…”