title: Characterization of protein tyrosine phosphatase H1 knockout mice in animal models of local and systemic inflammation.
abstract: BACKGROUND
  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, 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.
  
  
  METHODS
  We 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.
  
  
  RESULTS
  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 TNFalpha, 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.
  
  
  CONCLUSIONS
  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 in vivo, in contrast to previous reports indicating PTPH1 as potential negative regulator of immune response.
authors.affiliation: MerckSerono Ivrea, In vivo Pharmacology Department, via ribes 5, 10010 Colleretto G, (TO) Italy. claudia_patrignani@hotmail.com.
authors.forename: Claudia
authors.initials: C
authors.lastname: Patrignani
authors.forename: David T
authors.initials: DT
authors.lastname: Lafont
authors.forename: Valeria
authors.initials: V
authors.lastname: Muzio
authors.forename: Béatrice
authors.initials: B
authors.lastname: Gréco
authors.forename: Rob
authors.initials: R
authors.lastname: Hooft van Huijsduijnen
authors.forename: Paola F
authors.initials: PF
authors.lastname: Zaratin