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. 2014 May 5;111(20):7391–7396. doi: 10.1073/pnas.1403477111

Fig. 2.

Fig. 2.

RIP1 inhibition or deficiency protect macrophages from Y. pestis-induced cell death. (A) RIP1-deficient fetal liver macrophages are resistant to Y. pestis-induced killing (MOI 40, 4 h), detected by LDH release. (B and D) RIP1, but not RIP3, mediates caspase-8 enzymatic activity after infection of BMDM (D) or fetal liver macrophages (B) with Y. pestis for 2 h. (C) Caspase-8 conditional KO macrophages are protected from Y. pestis-induced death in the presence of RIP1 (GSK’963) or RIP3 (GSK’872) kinase inhibitors, but not by inactive compound GSK’962. (D) RIP1 kinase inhibitor GSK’963 inhibits caspase-8 enzyme activity after infection. (E) RIP1 forms a complex with caspase-8 upon infection (1 h), measured by co-IP. (F) RIP1 is cleaved after Y. pestis infection in a caspase-8 dependent fashion. Figures are representative for three to eight experiments performed. Bars indicate mean plus SD. **P < 0.01 (two-tailed t test).