Figure 1. TRPV4 channel blockade protects mice from the lethality of LPS and CLP, but not TNFα, in vivo.
(a) Seven-day survival of CLP model mice, without (CLP) or with (CLP + GSK219) GSK219; GSK219 (1 mg/kg, i.p.) was administered 1 hour prior to CLP (Sham, n = 5; CLP and CLP + GSK219, n = 12; *p < 0.05 vs. CLP alone, Mantel-Cox test). (b) Seven-day survival of mice injected with LPS only (50 mg/kg, i.p.) or LPS + GSK219; GSK219 (1 mg/kg, i.p.) was administered 1 hour prior to or 2 or 4 hours after LPS injection (n = 10 mice/group; *p < 0.05 vs. LPS treatment, Mantel-Cox test). (c) Seven-day survival of mice injected with LPS only (50 mg/kg, i.p.) or LPS + HC067; HC067 (10 mg/kg, i.p.) was administered 1 hour prior to or 2 hours after LPS injection (n = 10 mice/group; *p < 0.05 vs. LPS treatment, Mantel-Cox test). (d) Twenty-four-hour survival of mice injected with TNFα only (1 mg/kg, i.p.) or with TNFα + GSK219; GSK219 (1 mg/kg, i.p.) was administered 1 hour prior to TNFα injection (n = 10 mice/group; *p < 0.05 vs. TNFα treatment, Mantel-Cox test). (e) Seven-day survival of normal or TRPV4−/− mice injected with LPS only (50 mg/kg, i.p.) or TRPV4−/− mice injected with LPS + GSK219. GSK219 (1 mg/kg, i.p.) was administered 1 hour prior to LPS injection (n = 10 mice/group; *p < 0.05 vs. LPS treatment, Mantel-Cox test).