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Rheumatology Advance Access originally published online on August 27, 2009
Rheumatology 2009 48(11):1352-1358; doi:10.1093/rheumatology/kep235
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© The Author 2009. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org

TREM-1 expression is increased in the synovium of rheumatoid arthritis patients and induces the expression of pro-inflammatory cytokines

Jun Kuai1, Bernard Gregory2, Andrew Hill3, Debra D. Pittman4, Jeffrey L. Feldman4, Tom Brown5, Brenda Carito4, Margot O’Toole3, Renee Ramsey3, Oskar Adolfsson4, Kathleen M. Shields4, Ken Dower1, J. Perry Hall1, Yahya Kurdi1, Jonathan T. Beech2, Jagdeep Nanchahal2, Marc Feldmann2, Brian M. Foxwell2,{dagger}, Fionula M. Brennan2, David G. Winkler1 and Lih-Ling Lin1

1Department of Inflammation, Wyeth Research, Cambridge, MA, USA, 2Faculty of Medicine, Kennedy Institute of Rheumatology Division, Imperial College London, London, UK, 3Department of Biological Technology, 4Department of Cardiovascular and Metabolic Disease, Wyeth Research, Cambridge and 5Exporatory Drug Safety, Wyeth, Andover, MA, US.

Correspondence to: Lih-Ling Lin, Department of Inflammation, Wyeth Research, 200 Cambridge Park Drive, Cambridge, MA 02140, USA. E-mail: llin{at}wyeth.com


  Abstract

Objectives. To investigate the expression and function of triggering receptor expressed on myeloid cells-1 (TREM-1) in the synovium of human RA patients as well as the level of soluble TREM-1 in the plasma of RA patients.

Methods. Twenty-four RA synovial samples were analysed by gene expression oligonucleotide microarrays. Expression levels of TREM-1 mRNA in murine CIA paws were determined by quantitative PCR (qPCR). TREM-1 protein expression was detected by immunohistochemistry in five RA synovial samples and two OA synovial samples. TREM-1-positive cells from five RA synovial tissues were analysed by FACS staining to determine the cell type. Activation of TREM-1 was tested in five RA synovial samples. Soluble TREM-1 was measured in serum from 32 RA patients.

Results. The expression of TREM-1 mRNA was found to increase 6.5-fold in RA synovial samples, whereas it was increased 132-fold in CIA paws. Increased numbers of TREM-1-positive cells were seen in RA synovium sections and these cells co-expressed CD14. Using a TREM-1-activating cross-linking antibody in RA synovial cultures, multiple pro-inflammatory cytokines were induced. The average amount of soluble TREM-1 in plasma from RA patients was found to be higher than that in plasma from healthy volunteers.

Conclusions. These findings suggest that the presence of high levels of functionally active TREM-1 in RA synovium may contribute to the development or maintenance of RA, or both. Inhibiting TREM-1 activity may, therefore, have a therapeutic effect on RA. High levels of soluble TREM-1 in the plasma of RA patients compared with healthy volunteers may indicate disease activity.

KEY WORDS: Triggering receptor expressed on myeloid cells-1, DNAX-activation protein 12, Rheumatoid arthritis, RA synovium

Present address: Ken Dower, Whitehead Institute for Biomedical Research, Cambridge, MA, USA.

{dagger}deceased.

Submitted 25 March 2009; revised version accepted 6 July 2009.
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