Fig. 3: TAK-243 exacerbates inflammation in a RIPK3–CASP8-dependent manner.
From: Independent mechanisms of inflammation and myeloid bias in VEXAS syndrome
a, Rectal temperatures and survival of C57BL/6 mice after i.v. injection of TNF (200 μg per kg), pretreated 2 h before with either vehicle or TAK-243 (3 mg per kg i.p.), and 30 min before with either PBS or Nec-1s (6 mg per kg, i.v.). The mean rectal temperatures are shown for n = 10–15 mice per condition. b, Rectal temperatures and survival of Ripk1+/+ (n = 10) and Ripk1D138N/D138N (n = 8) mice after i.v. injection of TNF (200 μg per kg), pretreated 2 h before with TAK-243 (3 mg per kg, i.p.). c, Rectal temperatures and survival of bone-marrow chimeras of the indicated genotypes (n = 6–7 mice per cohort) after i.p. injection of LPS (5 mg per kg), pretreated 2 h before with vehicle or TAK-243 (3 mg per kg, i.p.). Experiments were performed 5 weeks after 10 Gy irradiation and bone marrow transplantation. P values comparing survival curves in a–c were calculated using the log-rank (Mantel–Cox) test; *P < 0.05, **P < 0.01, ***P < 0.001. For a–c, data are mean ± s.e.m.
