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-α)] and CC chemokines [monocyte chemoattractant protein (MCP- 1), macrophage inflammatory protein (MIP-1α), RANTES] in patients with rheumatoid arthritis (RA) and osteoarthritis (OA) and subjects after traumatic injury (PT). Methods. Articular cartilage specimens were obtained from 38 patients with OA and 18 with RA under- going joint replacement surgery. Healthy human cartilage 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-1β, tumor necrosis factor-α (TNF-α)] and antiinflammatory [transforming growth factor-β1 (TGF-β1), IL-l0] mediators. Chemokine concentrations in cell supernatants were evaluated by ELISA. Results. Chondrocytes produce all these chemokines to a different extent. IL-1β was a more potent stimulus than TNF- α in inducing production of all chemokines except MCP-1. We found no statistical differences among chondrocytes isolated from OA, RA, and PT for chemokine production in either basal conditions or after cytokine stimulation. IL-1β induced chemokine production can be modulated by TGF-β1 in different ways according to the various chemokines, while IL-10 does not affect IL-1β induced chemokine production. Conclusion. Chondrocytes produce IL-8, GRO-α, MCP-1, MIP-1α, and RANTES. Proinflammatory factors (IL-1β, TNF-α) effectively upregulate chemokine production, but production is scarcely modulated by the antiinflammatory mediators TGF-β and IL-10. Chondrocyte derived chemokines may play a role in triggering the mechanisms involved in pathogenesis and persistence of joint diseases.