Figure 4. SOCS1 mediates protective effects during sepsis via blockage of STAT3 activation.

Levels of Stat3 mRNA expression 18 hours after onset of sepsis as quantified by qPCR in peritoneal cells from inhibitor of the kinase inhibitory region–treated (iKIR-treated) septic mice (A) or Socs1^Δmyel septic mice (B). A: n = 3 mice/group, 1-way ANOVA followed by Bonferroni correction; B: n = 9–10 mice/group, t test. (C) Top: Lung cells were harvested 18 hours after induction of sepsis in mice treated with iKIR or control peptide and subjected to immunoblotting for determination of total STAT3 and phosphorylated STAT3 (Tyr705) expression. Bottom: Histogram showing mean densitometric analysis of immunoblots (n = 3–4 mice/group, 1-way ANOVA followed by Bonferroni correction). (D) Survival rates of iKIR-treated septic mice that were treated (or not) with STATTIC at 24 hours and 1 hour before cecal ligation and puncture (CLP) and once daily for 3 days after CLP (n = 7–8 mice/group, log-rank [Mantel-Cox] test). (E) Bacterial load in mice treated as in D. CFU determined 18 hours after CLP (n = 3–4 mice/group, 1-way ANOVA followed by Bonferroni correction). Scatter plot shows individual values, mean, and SEM. *P < 0.05, control septic mice vs. naive, Socs1^Δmyel septic mice vs. Socs1^fl; ^#P < 0.05, iKIR-treated septic mice vs. naive; ^%P < 0.05, STATTIC- and iKIR-treated septic mice vs. iKIR-treated septic mice; ^&P < 0.05, iKIR-treated septic mice vs. control septic mice.