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

<p>Abstract</p> <p>Background</p> <p>PTPH1 is a protein tyrosine phosphatase expressed in T cells but its effect on immune response is still controversial. PTPH1 dephosphorylates TCRzeta <it>in vitro</it>, inhibiting the downstream inflammatory signaling pat...

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Main Authors: Muzio Valeria (Author), Lafont David T (Author), Patrignani Claudia (Author), Gréco Béatrice (Author), van Huijsduijnen Rob (Author), Zaratin Paola F (Author)
Format: Book
Published: BMC, 2010-03-01T00:00:00Z.
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Summary:<p>Abstract</p> <p>Background</p> <p>PTPH1 is a protein tyrosine phosphatase expressed in T cells but its effect on immune response is still controversial. PTPH1 dephosphorylates TCRzeta <it>in vitro</it>, 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 <it>in vivo </it>inflammatory models and to give insights in possible PTPH1 functions in cytokine release.</p> <p>Methods</p> <p>We challenged PTPH1-KO mice with two potent immunomodulatory molecules, carrageenan and LPS, in order to determine PTPH1 possible role in inflammatory response <it>in vivo</it>. Cytokine release, inflammatory pain and gene expression were investigated in challenged PTPH1-WT and KO mice.</p> <p>Results</p> <p>The 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.</p> <p>Conclusion</p> <p>In 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 <it>in vivo</it>, in contrast to previous reports indicating PTPH1 as potential negative regulator of immune response.</p>
Item Description:10.1186/1476-9255-7-16
1476-9255