Fig. 3.

Increased death sensitization of Ikk2-deficient SFs in TNF-mediated signals. a Representative images depicting TUNEL+ or CC3+ cells in sections of Ikk2^f/f and Ikk2^Ms-KO mice (naive, hTNFtg (week8) or CAIA-treated (D8)) (n = 6 per genotype). Note the CC3+ cartilage cells (blue arrow), lining (black) and sublining (red) SFs, and other cells (open arrow) within necroptic areas. b Quantitation of TUNEL+ cells found in synovial membrane area of Ikk2^f/f and Ikk2^Ms-KO in naive (n = 5–7) and arthritic conditions (hTNFtg (n = 4–7); CAIA (n = 4)). c Survival rates of Ikk2^f/f, hTNFtg Ikk2^f/f SFs, and WT MEFs treated with different TNF concentrations, in the presence or absence of ML120b inhibitor (representative experiment, n = 5). d Representative immunoblot of IKK2 expression after the application of TAT-Cre in SF cultures derived from Ikk2^f/f and hTNFtg Ikk2^f/f mice, and IkB degradation and JNK1/2 phosphorylation patterns after TNF or IL-1β treatment of Ikk2-deficient SFs. Relative quantitations are depicted for each blot. e Representative survival rates of Ikk2^Δ/Δ and hTNFtg Ikk2^Δ/Δ SFs and Ikk2^−/− MEFs and control Ikk2^f/f and hTNFtg Ikk2^f/f SFs and WT MEFs treated with different TNF concentrations (n = 15, 4 experiments). Scale bar: 100 μm. Data are presented as the mean ± SEM. *P < 0.05, **P < 0.01, and ***P < 0.001, by two-tailed Student’s t-test (b) or one-way ANOVA (c, d). Unprocessed original scans of blots are shown in Supplementary Fig. 8