Chemokine production by human chondrocytes

Objective, To evaluate the role of chondrocytes in producing CXC chemokines [interleukin 8 (IL-8), growth related gene product (GRO-alpha)] and CC che mokines [monocyte chemoattractant protein (MCP-1), macrophage inflammatory protein (MIP-1 alpha), RANTES] in patients with rheumatoid arthritis (RA) a nd osteoarthritis (OA) and subjects after traumatic injury (PT). Methods. Articular cartilage specimens were obtained from 38 patients with OA and 18 with RA undergoing joint replacement surgery. Healthy human carti lage was obtained from femoral condyles removed after trauma in 11 subjects with no history of joint pathology (PT cases). Chondrocytes were isolated from articular cartilage by sequential enzymatic digestion and cultured in vitro. Chemokine production was investigated in unstimulated condition and after 72 h incubation with proinflammatory [IL-1 beta, tumor necrosis facto r-alpha (TNF-alpha)] and antiinflammatory [transforming growth factor-beta 1 (TGF-beta 1), IL-10] mediators. Chemokine concentrations in cell supernat ants were evaluated by ELISA. Results. Chondrocytes produce all these chemokines to a different extent. I L-1 beta was a more potent stimulus than TNF-alpha in inducing production o f all chemokines except MCP-1. We found no statistical differences among ch ondrocytes isolated from OA, RA, and PT for chemokine production in either basal conditions or after cytokine stimulation. IL-1 beta induced chemokine production can be modulated by TGF-beta 1 in different ways according to t he various chemokines, while IL-10 does not affect IL-1 beta induced chemok ine production. Conclusion. Chondrocytes produce IL-8, GRO-alpha, MCP-1, MIP-1 alpha, and R ANTES. Proinflammatory factors (IL-1 beta, TNF-alpha) effectively upregulat e chemokine production, but production is scarcely modulated by the antiinf lammatory mediators TGF-beta and IL-10. Chondrocyte derived chemokines may play a role in triggering the mechanisms involved in pathogenesis and persi stence of joint diseases.