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.
Highlights
PTPH1 is a protein tyrosine phosphatase expressed in T cells but its effect on immune response is still controversial
N = 7-8 animals per genotype were injected subcutaneously in the right hind paw plantar surface with 30 μL of a solution of 2% carrageenan λ (Sigma, Germany) freshly prepared in saline. 30 μL of saline were injected as control in the controlateral paw
Carrageenan (CARR)-induced inflammation Female WT and KO mice were subcutaneously injected in the right hind paw plantar surface with 2% carrageenan λ freshly prepared in saline. 30 μL of saline were injected as control in the controlateral paw
Summary
PTPH1 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, no immunological phenotype has been detected in primary T cells derived from PTPH1-KO mice. Tyrosine phosphorylation is a central mechanism in the control of key signaling proteins involved in innate immunity. SRC homology 2 (SH2)-containing tyrosine phosphatase (SHP-2) has a controversial effect on lymphocyte signaling.
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