Rheumatology Advance Access originally published online on August 27, 2007
Rheumatology 2007 46(10):1538-1546; doi:10.1093/rheumatology/kem198
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The expression of SOCS is altered in rheumatoid arthritis
1Institute of Medical Technology, University of Tampere, 2Department of Internal Medicine, Division of Rheumatology, 3Department of Pathology, 4Laboratory Centre, 5Department of Clinical Microbiology, Tampere University Hospital and 6Coxa, Hospital for Joint Replacement, Tampere, Finland.
Correspondence to: P. Isomäki, MD PhD, Department of Molecular Immunology, Institute of Medical Technology, Biokatu 8, 33014 Tampere University, Tampere, Finland. E-mail: pia.isomaki{at}uta.fi
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Abstract |
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Objectives. Cytokines play a key pathogenic role in rheumatoid arthritis (RA). Several cytokines signal through the JAK-STAT pathway, which is negatively regulated by the suppressors of cytokine signalling (SOCS) proteins. Since SOCS protein levels can profoundly modulate cellular responses to cytokines, we have investigated their expression in chronic RA.
Methods. The levels of SOCS1–3 and CIS1 mRNA in peripheral blood (PB) and synovial fluid (SF) mononuclear cells (MCs), purified T cells and monocytes from RA patients and healthy volunteers were studied using quantitative reverse transcriptase polymerase chain reaction (RT-PCR). SOCS mRNA and protein expression in synovial tissues were examined by RT-PCR and immunohistochemistry.
Results. The levels of SOCS1 and SOCS3 were significantly increased in PBMCs from RA patients when compared with healthy volunteers. These differences were mainly due to up-regulation of SOCS1 in PB T cells and of SOCS3 in PB monocytes. In addition, SOCS2 was up-regulated in PB T cells. Interestingly, SF T cells expressed lower and SF macrophages higher levels of SOCS molecules than their PB counterparts. Similarly, while a significant portion of macrophages in synovial tissues expressed SOCS1 and SOCS3 proteins, the majority of T cells remained SOCS negative. Finally, SOCS1 was up-regulated in the synovial membranes from patients with RA when compared with osteoarthritis.
Conclusions. SOCS expression levels are profoundly altered in RA, and the profile of SOCS expression is dependent on both the cell type as well as the cellular compartment.
KEY WORDS: Rheumatoid arthritis, Cytokines, Signal transduction, JAK-STAT pathway, SOCS proteins
Submitted 4 February 2007;
revised version accepted 18 June 2007.
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