PMID:15254593

Citation	Vowinkel, T, Mori, M, Krieglstein, CF, Russell, J, Saijo, F, Bharwani, S, Turnage, RH, Davidson, WS, Tso, P, Granger, DN and Kalogeris, TJ (2004) Apolipoprotein A-IV inhibits experimental colitis. J. Clin. Invest. 114:260-9
Abstract	The antiatherogenic properties of apoA-IV suggest that this protein may act as an anti-inflammatory agent. We examined this possibility in a mouse model of acute colitis. Mice consumed 3% dextran sulfate sodium (DSS) in their drinking water for 7 days, with or without daily intraperitoneal injections of recombinant human apoA-IV. apoA-IV significantly and specifically delayed the onset, and reduced the severity and extent of, DSS-induced inflammation, as assessed by clinical disease activity score, macroscopic appearance and histology of the colon, and tissue myeloperoxidase activity. Intravital fluorescence microscopy of colonic microvasculature revealed that apoA-IV significantly inhibited DSS-induced leukocyte and platelet adhesive interactions. Furthermore, apoA-IV dramatically reduced the upregulation of P-selectin on colonic endothelium during DSS-colitis. apoA-IV knockout mice exhibited a significantly greater inflammatory response to DSS than did their WT littermates; this greater susceptibility to DSS-induced inflammation was reversed upon exogenous administration of apoA-IV to knockout mice. These results provide the first direct support for the hypothesis that apoA-IV is an endogenous anti-inflammatory protein. This anti-inflammatory effect likely involves the inhibition of P-selectin-mediated leukocyte and platelet adhesive interactions.
Links	PubMed PMC450164 Online version:10.1172/JCI21233
Keywords	Animals; Anti-Inflammatory Agents/immunology; Anti-Inflammatory Agents/metabolism; Apolipoproteins A/genetics; Apolipoproteins A/immunology; Apolipoproteins A/metabolism; Colitis/chemically induced; Colitis/immunology; Colitis/metabolism; Colitis/pathology; Colon/anatomy & histology; Colon/pathology; Dextran Sulfate/administration & dosage; Dextran Sulfate/toxicity; Disease Models, Animal; Epithelial Cells/cytology; Epithelial Cells/metabolism; Humans; Indicators and Reagents/administration & dosage; Indicators and Reagents/toxicity; Inflammation/immunology; Inflammation/metabolism; Intestinal Mucosa/cytology; Intestinal Mucosa/metabolism; Intestinal Mucosa/pathology; Leukocytes/immunology; Leukocytes/metabolism; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; P-Selectin/metabolism; Platelet Adhesiveness/physiology; Recombinant Proteins/genetics; Recombinant Proteins/immunology; Recombinant Proteins/metabolism
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