Figure 1
(a) Blocking Cx channels by Gap27 protects mice against TNF-induced mortality and hypothermia. Cumulative survival rates and body temperatures as a function of time. Male C57BL/6J mice were injected i.v. with Gap27 (25 mg/kg) or vehicle (DPBS) 15 min prior to i.v. injection of TNF (LD100). Pool of 2 independent experiments. The one-star differences in the left and right panel have p-values of 0.0212 and 0.0338, respectively; **p = 0.0043, ****p < 0.0001. (b,c) Blocking Cx43 hemichannels protects mice against TNF-induced mortality, hypothermia and renal vascular permeability alterations. Male C57BL/6J mice were pre-injected i.v. with the indicated peptides 15 min prior to i.v. injection of TNF (LD70); n = total number of mice per group. (b) Cumulative survival rates and body temperatures presented as a function of time. Pool of 4 independent experiments. A significant protection is observed upon selective Cx43 hemichannel blockade by TAT-Gap19, when compared to pre-treatment with vehicle (**p = 0.0022) or TAT (**p = 0.0067). The two-star difference (right panel) equals a p-value of 0.0019; ****p < 0.0001. LD70 = lethal dose for 70% of mice in control group (Vehicle + TNF). (c) Vascular permeability shown as relative light units (RLU) of FITC-dextran in colon, ileum, lungs and kidneys 6 hr after injection of vehicle or TNF. Pool of 2 independent experiments. The two-star difference corresponds to a p-value of 0.0073; ****p < 0.0001. (d,e) Stimulating Cx43 hemichannel opening accelerates TNF-induced mortality, hypothermia and vascular permeability increase. Male C57BL/6J mice were pre-injected i.v. with the indicated peptides 15 min prior to i.v. injection of a sub-lethal dose of TNF (LD0); n = total number of mice per group. (d) Survival and body temperature presented as a function of time. Mice receiving TAT-CT9 are sensitized towards TNF-induced lethality, when compared to mice pre-treated with TAT-Gap19 (**p = 0.0074), TAT (**p = 0.0034) and 10 mg/kg TAT-Gap19 + TAT-CT9 (**p = 0.0034) (d; left panel). The two-star difference in (d; right panel) corresponds to a p-value of 0.0078; ****p < 0.0001. LD0 = non-lethal dose for mice in control group (TAT + TNF). (e) Vascular permeability shown as RLU of FITC-dextran in colon, ileum, lungs and kidneys 6 hr after injection of vehicle or TNF. The one-star difference corresponds to a p-value of 0.0256, the two-star difference has a p-value of 0.0077. Data are presented as mean ± SEM. Statistical tests used: (a (left), b (left), d (left)): Mantel-Cox test; a (right): 2-Way ANOVA with post-hoc Sidak's test; (b (right), c,d (right), e): 2-Way ANOVA with post-hoc Tukey’s test.
