Apolipoprotein A-IV inhibits experimental colitis.

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.

• Authors: Thorsten Vowinkel, Mikiji Mori, Christian F Krieglstein, Janice Russell, Fumito Saijo, Sulaiman Bharwani, Richard H Turnage, W Sean Davidson, Patrick Tso, D Neil Granger, Theodore J Kalogeris
• Journal: The Journal of clinical investigation (J Clin Invest) Vol. 114 Issue 2 Pg. 260-9 (Jul 2004) ISSN: 0021-9738 [Print] United States
• PMID: 15254593 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Anti-Inflammatory Agents
• Apolipoproteins A
• Indicators and Reagents
• P-Selectin
• Recombinant Proteins
• apolipoprotein A-IV
• Dextran Sulfate

Topics

• Animals
• Anti-Inflammatory Agents (immunology, metabolism)
• Apolipoproteins A (genetics, immunology, metabolism)
• Colitis (chemically induced, immunology, metabolism, pathology)
• Colon (anatomy & histology, pathology)
• Dextran Sulfate (administration & dosage, toxicity)
• Disease Models, Animal
• Epithelial Cells (cytology, metabolism)
• Humans
• Indicators and Reagents (administration & dosage, toxicity)
• Inflammation (immunology, metabolism)
• Intestinal Mucosa (cytology, metabolism, pathology)
• Leukocytes (immunology, metabolism)
• Male
• Mice
• Mice, Inbred C57BL
• Mice, Knockout
• P-Selectin (metabolism)
• Platelet Adhesiveness (physiology)
• Recombinant Proteins (genetics, immunology, metabolism)