Expression and production of the long pentraxin PTX3 in rheumatoid arthritis (RA)

PTX3 is a secreted molecule which consists of a C-terminal domain similar t o classical pentraxins (e.g. C-reactive protein (CRP)) and of an unrelated N-terminal domain. Unlike the classical pentraxins, the long pentraxin PTX3 is expressed in response to IL-1 beta and tumour necrosis factor-alpha (TN F-alpha), but not to IL-6, in various cell types. The present study was des igned to investigate the expression of PTX3 in RA. Dissociated RA and osteo arthritis (OA) type B synoviocytes were cultured in the presence and in the absence of inflammatory cytokines. PTX3 mRNA expression in synoviocytes wa s evaluated by Northern analysis. PTX3 protein levels in synovial cell cult ures and synovial fluid were estimated by ELISA, and PTX3 distribution in s ynovial tissues by immunohistochemical techniques. OA synoviocytes were ind uced to express high levels of PTX3 mRNA by TNF-alpha, but not by other cyt okines including IL-1 beta and IL-6. RA synoviocytes, unlike OA synoviocyte s, constitutively expressed high levels of PTX3 in the absence of deliberat e stimulation. The constitutive expression of PTX3 in RA synoviocytes was n ot modified by anti-TNF-alpha antibodies, IL-1 receptor antagonist or a com bination of the two agents. In contrast, interferon-gamma and transforming growth factor-beta inhibited PTX3 constitutive expression in RA synoviocyte s. The joint fluid from RA patients contained higher levels of immunoreacti ve PTX3 than controls and the synovial tissue contained endothelial cells a nd synoviocytes positive for PTX3 by immunohistochemistry. In conclusion, P TX3 may play a role in inflammatory circuits of RA, and its relevance as a marker of disease activity deserves further study.