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Apolipoprotein A-IV inhibits experimental colitis.

Authors: Vowinkel, T  Mori, M  Krieglstein, CF  Russell, J  Saijo, F  Bharwani, S  Turnage, RH  Davidson, WS  Tso, P  Granger, DN  Kalogeris, TJ 
Citation: Vowinkel T, etal., J Clin Invest. 2004 Jul;114(2):260-9.
Pubmed: (View Article at PubMed) PMID:15254593
DOI: Full-text: DOI:10.1172/JCI21233

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.

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CRRD Object Information
CRRD ID: 5685667
Created: 2012-01-16
Species: All species
Last Modified: 2012-01-16
Status: ACTIVE



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