Enhancing Effect of IL-1, IL-17, and TNF-α on Macrophage Inflammatory Protein-3α Production in Rheumatoid Arthritis: Regulation by Soluble Receptors and Th2 Cytokines

  • Chabaud M
  • Page G
  • Miossec P
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Abstract

Macrophage inflammatory protein (MIP)-3α is a chemokine involved in the migration of T cells and immature dendritic cells. To study the contribution of proinflammatory cytokines and chemokines to the recruitment of these cells in rheumatoid arthritis (RA) synovium, we looked at the effects of the monocyte-derived cytokines ΙL-1β and TNF-α and the T cell-derived cytokine IL-17 on MIP-3α production by RA synoviocytes. Addition of ΙL-1β, IL-17, and TNF-α induced MIP-3α production in a dose-dependent manner. At optimal concentrations, ΙL-1β (100 pg/ml) was much more potent than IL-17 (100 ng/ml) and TNF-α (100 ng/ml). When combined at lower concentrations, a synergistic effect was observed. Conversely, the anti-inflammatory cytokines IL-4 and IL-13 inhibited MIP-3α production by activated synoviocytes, but IL-10 had no effect. Synovium explants produced higher levels of MIP-3α in RA than osteoarthritis synovium. MIP-3α-producing cells were located in the lining layer and perivascular infiltrates in close association with CD1a immature dendritic cells. Addition of exogenous IL-17 or ΙL-1β to synovium explants increased MIP-3α production. Conversely, specific soluble receptors for ΙL-1β, IL-17, and TNF-α inhibited MIP-3α production to various degrees, but 95% inhibition was obtained only when the three receptors were combined. Similar optimal inhibition was also obtained with IL-4, but IL-13 and IL-10 were less active. These findings indicate that interactions between monocyte and Th1 cell-derived cytokines contribute to the recruitment of T cells and dendritic cells by enhancing the production of MIP-3α by synoviocytes. The inhibitory effect observed with cytokine-specific inhibitors and Th2 cytokines may have therapeutic applications.

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APA

Chabaud, M., Page, G., & Miossec, P. (2001). Enhancing Effect of IL-1, IL-17, and TNF-α on Macrophage Inflammatory Protein-3α Production in Rheumatoid Arthritis: Regulation by Soluble Receptors and Th2 Cytokines. The Journal of Immunology, 167(10), 6015–6020. https://doi.org/10.4049/jimmunol.167.10.6015

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