title: Differential expression of CD148 on leukocyte subsets in inflammatory arthritis.
abstract: BACKGROUND
  Monocytic cells play a central role in the aetiology of rheumatoid arthritis, and manipulation of the activation of these cells is an approach currently under investigation to discover new therapies for this and associated diseases. CD148 is a transmembrane tyrosine phosphatase that is highly expressed in monocytes and macrophages and, since this family of molecules plays an important role in the regulation of cell activity, CD148 is a potential target for the manipulation of macrophage activation. For any molecule to be considered a therapeutic target, it is important for it to be increased in activity or expression during disease.
  
  
  METHODS
  We have investigated the expression of CD148 in two murine models of arthritis and in joints from rheumatoid arthritis (RA) patients using real-time PCR, immunohistochemistry, and studied the effects of proinflammatory stimuli on CD148 activity using biochemical assays.
  
  
  RESULTS
  We report that CD148 mRNA is upregulated in diseased joints of mice with collagen-induced arthritis. Furthermore, we report that in mice CD148 protein is highly expressed in infiltrating monocytes of diseased joints, with a small fraction of T cells also expressing CD148. In human arthritic joints both T cells and monocytes expressed high levels of CD148, however, we show differential expression of CD148 in T cells and monocytes from normal human peripheral blood compared to peripheral blood from RA and both normal and RA synovial fluid. Finally, we show that synovial fluid from rheumatoid arthritis patients suppresses CD148 phosphatase activity.
  
  
  CONCLUSIONS
  CD148 is upregulated in macrophages and T cells in human RA samples, and its activity is enhanced by treatment with tumour necrosis factor alpha (TNFα), and reduced by synovial fluid or oxidising conditions. A greater understanding of the role of CD148 in chronic inflammation may lead to alternative therapeutic approaches to these diseases.
authors.forename: Richa K
authors.initials: RK
authors.lastname: Dave
authors.forename: Amy J
authors.initials: AJ
authors.lastname: Naylor
authors.forename: Stephen P
authors.initials: SP
authors.lastname: Young
authors.forename: Rachel
authors.initials: R
authors.lastname: Bayley
authors.forename: Debbie L
authors.initials: DL
authors.lastname: Hardie
authors.forename: Oliver
authors.initials: O
authors.lastname: Haworth
authors.forename: David A
authors.initials: DA
authors.lastname: Rider
authors.forename: Andrew D
authors.initials: AD
authors.lastname: Cook
authors.forename: Christopher D
authors.initials: CD
authors.lastname: Buckley
authors.forename: Stuart
authors.initials: S
authors.lastname: Kellie
mesh_terms: D000818:Animals; D001169:Arthritis, Experimental / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D001172:Arthritis, Rheumatoid / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D020869:Gene Expression Profiling; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology; D007150:Immunohistochemistry; D007596:Joints / Q000378:metabolism / Q000473:pathology; D007963:Leukocytes, Mononuclear / Q000378:metabolism* / Q000473:pathology; D008264:Macrophages / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D018613:Microscopy, Confocal; D009000:Monocytes / Q000378:metabolism / Q000473:pathology; D016877:Oxidants / Q000494:pharmacology; D054631:Receptor-Like Protein Tyrosine Phosphatases, Class 3 / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013582:Synovial Fluid / Q000378:metabolism; D013601:T-Lymphocytes / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D015854:Up-Regulation
chemical_list: D016877:Oxidants; D014409:Tumor Necrosis Factor-alpha; D006861:Hydrogen Peroxide; C486288:PTPRJ protein, human; C098066:Ptprj protein, mouse; D054631:Receptor-Like Protein Tyrosine Phosphatases, Class 3
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