TREM-1 expression is increased in the synovium of rheumatoid arthritis patients and induces the expression of pro-inflammatory cytokines
| Autor: | Oskar Adolfsson, Marc Feldmann, Jonathan T Beech, J. Perry Hall, Brenda A. Carito, Brian M. J. Foxwell, David Winkler, Jun Kuai, Jagdeep Nanchahal, Debra D Pittman, Andrew A. Hill, Tom Brown, Margot O'Toole, Ken Dower, Bernard Gregory, Jeffrey L. Feldman, Fionula M. Brennan, Renee Ramsey, Yahya Kurdi, Lih-Ling Lin, Kathleen M. Shields |
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| Jazyk: | angličtina |
| Rok vydání: | 2009 |
| Předmět: |
Male
medicine.medical_treatment CD14 Gene Expression Arthritis Polymerase Chain Reaction Proinflammatory cytokine Arthritis Rheumatoid Mice Rheumatology medicine Animals Humans Pharmacology (medical) RNA Messenger Receptors Immunologic Cells Cultured Oligonucleotide Array Sequence Analysis Autoimmune disease Membrane Glycoproteins biology business.industry Gene Expression Profiling Synovial Membrane medicine.disease Arthritis Experimental Triggering Receptor Expressed on Myeloid Cells-1 medicine.anatomical_structure Real-time polymerase chain reaction Cytokine Mice Inbred DBA Immunology biology.protein Cytokines Inflammation Mediators Synovial membrane Antibody business Biomarkers |
| Zdroj: | Scopus-Elsevier |
| ISSN: | 1462-0332 1462-0324 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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