Thioredoxin (Trx) plays several important roles, through changes to sulfhydryl reactions and protein interactions, in controlling cellular signalling processes in RA (rheumatoid arthritis). Trx80, the 10 kDa C-terminal truncated form of Trx, is a potent mitogenic cytokine and is involved in the Th1 response. In the present study, we have investigated the ability of synoviocytes from five RA patients to induce Trx80 after ex vivo stimulation by the pro-inflammatory cytokines IL-1β (interleukin-1β) and TNF-α (tumour necrosis factor-α) or by H2O2. Synoviocytes from five OA (osteoarthritis) patients were used as controls. Immunoprecipitation assays using two different antibodies showed that RA, but not OA, cells expressed intact Trx80 protein in culture even when not stimulated. Treatment with pro-inflammatory cytokines alone or in combination enhanced this basal production and induced the extracellular release of Trx80 by all of the RA cells tested. Under our experimental conditions, the rate of Trx80 release from RA cells was approx. 30% of the total Trx produced. In contrast, Trx80 was not detected in response to H2O2 in RA or OA synoviocyte lysates and their respective culture supernatants, indicating that the oxidative process induced by H2O2 in synoviocytes was unable to modify Trx80 release. Moreover, Trx80 induced synoviocyte proliferation as evaluated by [3H]thymidine incorporation. These results highlight the effect of the inflammatory process on the release of both Trx and Trx80 from RA synoviocytes, and suggest that the cytokine-induced increase in Trx80 cell release may constitute a link between inflammation and the immune system in RA.
Expression and extracellular release of Trx80, the truncated form of thioredoxin, by TNF-α- and IL-1β-stimulated human synoviocytes from patients with rheumatoid arthritis
- Views Icon Views
- Share Icon Share
Hervé Lemarechal, Phillippe Anract, Jean-Louis Beaudeux, Dominique Bonnefont-Rousselot, Ohvanesse G. Ekindjian, Didier Borderie; Expression and extracellular release of Trx80, the truncated form of thioredoxin, by TNF-α- and IL-1β-stimulated human synoviocytes from patients with rheumatoid arthritis. Clin Sci (Lond) 1 August 2007; 113 (3): 149–155. doi: https://doi.org/10.1042/CS20070067
Download citation file: