Genetic deletion of Sphk1 amplifies lung inflammation and lethality in mice.

Abstract

<p>(<b>A</b>) Lung MPO activity. <i>Sphk1</i>^+/+ or <i>Sphk1^−/−</i> (n = 10 per time point of each genotype) mice were given LPS i.p. (0.5 mg/kg) and lungs were removed at the indicated times. Error bars represent s.d. *p<0.01 by Student's t-test. (<b>B, C</b>) Increased LPS-induced cytokine and chemokine production. TNF-α, IL-6, IL-1β, and KC were measured in plasma (<b>B</b>) and TNF-α, IL-6 and KC in lung tissue lysates (<b>C</b>) from <i>Sphk1</i>^+/+ or <i>Sphk1^−/−</i> mice, 1 h after i.p. LPS or saline injection. Error bars represent s.d. *p<0.05 by Student's t-test; n = 5 for each genotype. (<b>D</b>) Increased LPS-induced lethality. <i>Sphk1</i>^+/+ or <i>Sphk1^−/−</i> mice (n = 10/genotype, representative of three independent experiments) were given LPS i.p. (<b>E</b>) Increased LPS-induced lethality. <i>Sphk1</i>^+/+ or <i>Sphk1^−/−</i> mice (n = 10/genotype, representative of three independent experiments) were given LPS i.p. Differences in mortality were assessed by log-rank test (p<0.05). UD, undetected.</p