Fig. 1.

Influence of WIN55212-2 mesylate (WIN, 10⁻¹²M to 10⁻⁶M) with and without antagonists on TNF-induced IL-6 (a-f), IL-8 (g-l) and MMP-3 (m-r) production in RA and OA synovial fibroblasts. Cytokine/MMP-3 production was determined under hypoxic (1 % O₂) conditions. ***p < 0.001 for comparisons vs control (TNF only, 100 %, dotted line). ###p < 0.001, ##p < 0.01 for comparisons vs WIN/TNF only w/o antagonists. The general linear model with Bonferroni correction was used for all comparisons. All data are given as mean ± sem. CB₁ antagonist = CP945598, 1 μM; CB₂ antagonist = JTE-907, 1 μM; TRPV1 antagonist = capsazepine, 1 μM; TRPA1 antagonist = A967079, 1 μM; AMPK activator = metformin, 10 μM