Fig. 6: APIP exacerbates systemic inflammation in mice.

a–d Effects of APIP conditional-KO on systemic inflammation. Control and Apip cKO mice (10–11-weeks-old, n = 13 mice per group) were intraperitoneally injected with LPS (E. coli O111:B4, 15 mg/kg). Survival (a) and body temperature (b) were monitored. Control and Apip cKO mice (female, 10–12 weeks) were injected with LPS (15 mg/kg, 8 h), and serum IL-1β and TNF were quantified by ELISA (c, d). e–h Effects of APIP overexpression on systemic inflammation. WT and APIP^TG/+ mice (male, 9 weeks, n = 6 mice per group) were injected with LPS (E. coli O55:B5, 20 mg/kg). Survival (e) and body temperature (f) were monitored. WT and APIP^TG/+ mice (10–12 weeks) were injected with LPS (15 mg/kg, 8 h) alone or with C25-140 (14 mg/kg, three doses at 12 h intervals, last dose 4 h before LPS) (g, h). MCC950 (10 mg/kg) was administered 1 h before and 3.5 h after LPS, followed by 4.5 h incubation (g). Serum IL-1β (g) and TNF (h) were quantified by ELISA. i Serum IL-1β levels in mice co-injected with LPS and MSU. WT, control, and Apip cKO mice (10–12 weeks) were injected with LPS (1.5 mg/kg), followed 4 h later by MSU crystals (50 mg/kg). After 12 h, serum IL-1β was quantified by ELISA. j–m In vivo effects of APIP conditional-KO on bacterial sepsis. Control and Apip cKO mice (10–12 weeks, n = 8 mice) received fecal suspension injection (FSI, 1000 mg/kg). Survival (j) and body temperature (k) were monitored. Control and Apip cKO mice (10–12 weeks) received FSI (1000 mg/kg, 8 h), and serum IL-1β and TNF were quantified by ELISA (l, m). Data, except for survival graphs, represent mean + or ± SD (n = 3–13 mice per group; exact n values shown on the graphs/Source Data). Source data are provided as a Source Data file. Statistical tests: Log-rank test (a, e, j), two-way ANOVA with Sidak’s (b, f, k) or Tukey’s multiple comparison test (g, i), or unpaired two-tailed Student’s t-test (c, d, h, l, m).