Differential Expression of CD148 on leucocyte subsets in inflammatory arthritis

TY - JOUR

T1 - Differential Expression of CD148 on leucocyte subsets in inflammatory arthritis

AU - Dave, Richa

AU - Naylor, Amy

AU - Young, Stephen P.

AU - Bayley, Rachel

AU - Hardie, Debbie

AU - Haworth, Oliver

AU - Rider, David

AU - Cook, Andrew

AU - Buckley, Christopher

AU - Kellie, S

PY - 2013/9/9

Y1 - 2013/9/9

N2 - Introduction. 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 which 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 realtime 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 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 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.

AB - Introduction. 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 which 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 realtime 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 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 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.

UR - http://www.scopus.com/inward/record.url?eid=2-s2.0-84883547128&partnerID=MN8TOARS

U2 - 10.1186/ar4288

DO - 10.1186/ar4288

M3 - Article

VL - 15

JO - Arthritis Research & Therapy

JF - Arthritis Research & Therapy

SN - 1478-6354

IS - 5

M1 - R108

ER -