Rheumatology Advance Access originally published online on January 23, 2009
Rheumatology 2009 48(3):293-298; doi:10.1093/rheumatology/ken495
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The soluble terminal complement complex (SC5b-9) up-regulates osteoprotegerin expression and release by endothelial cells: implications in rheumatoid arthritis
1Interdepartmental Center of Molecular Medicine, University of Trieste, Trieste, 2Department of Morphology and Embryology, University of Ferrara, Ferrara, 3Department of Human Pathology, University of Palermo, Palermo, 4Rheumatology Section, Department of Clinical and Experimental Medicine, University of Ferrara, Ferrara, Italy and 5Institute of Immunology, Rikshospitalet University Hospital, Oslo, Norway.
Correspondence to: Paola Secchiero, Department of Morphology and Embryology, University of Ferrara, Via Fossato di Mortara 66, 44100 Ferrara, Italy. E-mail: paola.secchiero{at}unife.it
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Abstract |
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Objective. Complement activation products contribute to a large number of inflammatory diseases, including RA. We have investigated whether osteoprotegerin (OPG) may concur with the soluble terminal complement complex (SC5b-9) to the inflammatory cascade characterizing RA.
Methods. Levels of SC5b-9 and OPG in the plasma and SF of patients with active RA were determined by ELISA. The presence of SC5b-9 and OPG in RA synovial lesions was analysed by immunohistochemistry. Cultured endothelial cells were used for in vitro leucocyte/endothelial cell adhesion assays. In addition, endothelial cells were exposed to SC5b-9 in order to evaluate the effects on the production of OPG protein, as well as the activation of the OPG promoter.
Results. Patients affected by active RA are characterized by elevated levels of both SC5b-9 and OPG in plasma and/or SF. Of note, we have observed a co-localization of SC5b-9 and OPG in endothelial cells of post-capillary venules of RA synovial lesions. Data on endothelial cell cultures showed that exposure to SC5b-9 induced the up-regulation of OPG expression/release, stimulating the transcriptional activity of the OPG promoter, and synergized with TNF-
in up-regulating OPG production.
Conclusions. Our findings demonstrate that SC5b-9 induces OPG production by endothelial cells and we propose that the SC5b-9-mediated up-regulation of OPG may be an important mechanism whereby complement contributes in promoting and/or enhancing the inflammation in RA.
KEY WORDS: Endothelium, Osteoprotegerin, Inflammation, Complement system
*Federica Corallini and Fleur Bossi equally contributed to this work.
Submitted 7 October 2008;
revised version accepted 5 December 2008.
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