Expression and extracellular release of Trx80, the truncated form of thioredoxin, by TNF-{alpha} and IL-1 {beta}-stimulated human synoviocytes from patients with rheumatoid arthritis
Résumé
Thioredoxin (Trx) plays several important roles through changes to sulfhydryl reactions and protein interactions in controlling the cellular signaling process in rheumatoid arthritis (RA). The 10-kDa C-terminal truncated form of thioredoxin (Trx80) is a potent mitogenic cytokine and is involved in the Th1 response. We have investigated the ability of synoviocytes from five RA patients to induce the Trx80 form, after ex vivo stimulation by the pro-inflammatory cytokines IL-1β and TNF-α or by hydrogen peroxide (H 2}O 2}). Synovial cells from five osteoarthritis (OA) patients were used as controls. Immunoprecipitation assays using two different antibodies showed that RA but not OA cells expressed intact Trx80 protein even when not stimulated in culture. Treatments with pro-inflammatory cytokines alone or in combination enhanced this basal production and induced extracellular release of the truncated Trx80 form by all RA cells tested. Under our experimental conditions, the rate of Trx80 release from RA cells was approximately 30% of total Trx production. By contrast, Trx80 was not detected in RA and OA cell lysates and their respective culture supernatants in response to H 2}O 2}, indicating that the oxidative process induced by hydrogen peroxide in synoviocytes was unable to modify Trx80 release. Moreover, Trx80 induced synovial cell proliferation evaluated by tritiated thymidine incorporation. These results highlight the effect of the inflammatory process on the release of both Trx and Trx80 from synoviocytes in RA, and suggest that the cytokine-induced elevation of Trx80 cell release may constitute a link between inflammation and the immune system in RA disease.
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