title: 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.affiliation: Department of Molecular and Cellular Physiology, Louisiana State University Health Sciences Center, Shreveport 71130-3932, USA.
authors.forename: Thorsten
authors.initials: T
authors.lastname: Vowinkel
authors.forename: Mikiji
authors.initials: M
authors.lastname: Mori
authors.forename: Christian F
authors.initials: CF
authors.lastname: Krieglstein
authors.forename: Janice
authors.initials: J
authors.lastname: Russell
authors.forename: Fumito
authors.initials: F
authors.lastname: Saijo
authors.forename: Sulaiman
authors.initials: S
authors.lastname: Bharwani
authors.forename: Richard H
authors.initials: RH
authors.lastname: Turnage
authors.forename: W Sean
authors.initials: WS
authors.lastname: Davidson
authors.forename: Patrick
authors.initials: P
authors.lastname: Tso
authors.forename: D Neil
authors.initials: DN
authors.lastname: Granger
authors.forename: Theodore J
authors.initials: TJ
authors.lastname: Kalogeris
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000276:immunology / Q000378:metabolism*; D001054:Apolipoproteins A / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D003092:Colitis / Q000139:chemically induced / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D003106:Colon / Q000033:anatomy & histology / Q000473:pathology; D016264:Dextran Sulfate / Q000008:administration & dosage / Q000633:toxicity; D004195:Disease Models, Animal; D004847:Epithelial Cells / Q000166:cytology / Q000378:metabolism; D006801:Humans; D007202:Indicators and Reagents / Q000008:administration & dosage / Q000633:toxicity; D007249:Inflammation / Q000276:immunology / Q000378:metabolism; D007413:Intestinal Mucosa / Q000166:cytology / Q000378:metabolism / Q000473:pathology; D007962:Leukocytes / Q000276:immunology / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D019007:P-Selectin / Q000378:metabolism; D010973:Platelet Adhesiveness / Q000502:physiology; D011994:Recombinant Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism
chemical_list: D000893:Anti-Inflammatory Agents; D001054:Apolipoproteins A; D007202:Indicators and Reagents; D019007:P-Selectin; D011994:Recombinant Proteins; C022205:apolipoprotein A-IV; D016264:Dextran Sulfate