PT  - JOURNAL ARTICLE
AU  - M Kitagawa
AU  - H Suzuki
AU  - Y Adachi
AU  - H Nakamura
AU  - S Yoshino
AU  - T Sumida
TI  - Interferon-gamma enhances interleukin 12 production in rheumatoid synovial cells via CD40-CD154 dependent and independent pathways.
DP  - 2001 Aug 01
TA  - The Journal of Rheumatology
PG  - 1764--1771
VI  - 28
IP  - 8
4099  - http://www.jrheum.org/content/28/8/1764.short
4100  - http://www.jrheum.org/content/28/8/1764.full
SO  - J Rheumatol2001 Aug 01; 28
AB  - OBJECTIVE: To determine the role of interferon-gamma (IFN-gamma) in CD40-CD154 dependent production of interleukin 12 (IL-12) by synovial cells of patients with rheumatoid arthritis (RA). METHODS: We examined the effects of IFN-gamma, tumor necrosis factor-alpha (TNF-alpha), and granulocyte-macrophage colony stimulating factor (GM-CSF) on CD40 expression on CD68+ synovial macrophage-lineage cells (SMC). The effects of IFN-gamma and soluble CD154 (sCD154) on IL-12 production by RA synovial cells were determined by ELISA. RESULTS: CD68+ SMC expressed substantial levels of CD40. IFN-gamma, but not TNF-alpha or GM-CSF, markedly upregulated CD40 expression on CD68+ SMC. IFN-gamma also dose dependently increased IL-12 production by synovial cells. The effects of IFN-gamma on CD40 expression (EC50 = 127.4 U/ml) were observed at a concentration 19 times lower than the effects on IL-12 production (EC50 = 6.8 U/ml). Treatment with IFN-gamma at a concentration low enough to augment CD40 expression but not IL-12 production enhanced spontaneous IL-12 production synergy with sCD 154. The synergistic enhancement of spontaneous IL-12 production was abrogated by CD40-Fc. In contrast, IL-12 production induced by high concentration of IFN-gamma was not neutralized by CD40-Fc. CONCLUSION: IFN-gamma enhanced IL-12 production via both CD40-CD154 dependent and independent pathways in RA synovium. IFN-gamma may play a crucial role in the development of RA synovitis through regulation of IL-12 production.