A, IL-18 induces CF migration. At 70–80% confluence, CF were made quiescent by incubating in medium supplemented with 0.5% BSA for 48h. The quiescent CF were trypsinized, re-suspended in medium containing 0.5% BSA, layered on Matrigel™ basement membrane matrix-coated filters, and then treated with recombinant mouse IL-18 (10 ng/ml for 12 h). The lower chamber contained similar levels of IL-18. Specificity of IL-18 was verified by incubating the cells with IL-18A-neutralizing antibodies or IL-18BP-Fc (10 µg/ml) for 1 h prior to IL-18 addition. Cells migrating to the other side of the membrane were quantified using MTT assay. *P < 0.001 vs. untreated; †P< 0.01 vs. IL-17A (n=6). B, TRAF3IP2 gene deletion blunts IL-18-induced CF migration. CF isolated from WT and TRAF3IP2-null mice were made quiescent, and analyzed for IL-18-induced migration as in A. Lack of TRAF3IP2 expression was confirmed by immunoblotting (inset). *P< at least 0.01 vs. respective untreated; †P< 0.05 vs. WT-IL-18; (n=6). C, TRAF3IP2 gene deletion does not modify basal IL-18R subunit expression. CF isolated from TRAF3IP2-null mice or WT controls were made quiescent, and analyzed for IL-18Rα and IL-18Rβ expression by immunoblotting using cleared whole cell homogenates (n=3).