Differential expression of CD148 on leukocyte subsets in inflammatory arthritis

Dave, Richa K., Naylor, Amy J., Young, Stephen P., Bayley, Rachel, Hardie, Debbie L., Haworth, Oliver, Rider, David A., Cook, Andrew D., Buckley, Christopher D. and Kellie, Stuart (2013) Differential expression of CD148 on leukocyte subsets in inflammatory arthritis. Arthritis Research and Therapy, 15 5: R108.1-R108.13. doi:10.1186/ar4288

Author Dave, Richa K.
Naylor, Amy J.
Young, Stephen P.
Bayley, Rachel
Hardie, Debbie L.
Haworth, Oliver
Rider, David A.
Cook, Andrew D.
Buckley, Christopher D.
Kellie, Stuart
Title Differential expression of CD148 on leukocyte subsets in inflammatory arthritis
Journal name Arthritis Research and Therapy   Check publisher's open access policy
ISSN 1478-6354
Publication date 2013-09-09
Sub-type Article (original research)
DOI 10.1186/ar4288
Open Access Status DOI
Volume 15
Issue 5
Start page R108.1
End page R108.13
Total pages 13
Place of publication London, United Kingdom
Publisher BioMed Central
Collection year 2014
Language eng
Formatted abstract
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 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.
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2014 Collection
School of Chemistry and Molecular Biosciences
Institute for Molecular Bioscience - Publications
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