We investigated the effects of LASSBio-998 (L-998), a compound designed to be a p38 MAPK (mitogen-activated protein kinase) inhibitor, on lipopolysaccharide (LPS)-induced acute lung inflammation in vivo. BALB/c mice were challenged with aerosolized LPS inhalation (0.5 mg/ml) 4 h after oral administration of L-998.
View Article and Find Full Text PDFLow-grade polymicrobial infection induced by cecal ligation and puncture is lethal in heme oxygenase-1-deficient mice (Hmox1(-/-)), but not in wild-type (Hmox1(+/+)) mice. Here we demonstrate that the protective effect of this heme-catabolizing enzyme relies on its ability to prevent tissue damage caused by the circulating free heme released from hemoglobin during infection. Heme administration after low-grade infection in mice promoted tissue damage and severe sepsis.
View Article and Find Full Text PDF