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Apolipoprotein A-IV inhibits experimental colitis
Thorsten Vowinkel, … , D. Neil Granger, Theodore J. Kalogeris
Thorsten Vowinkel, … , D. Neil Granger, Theodore J. Kalogeris
Published July 15, 2004
Citation Information: J Clin Invest. 2004;114(2):260-269. https://doi.org/10.1172/JCI21233.
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Categories: Article Immunology

Apolipoprotein A-IV inhibits experimental colitis

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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

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Figure 1

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Western blot analysis of circulating apoA-IV. Serum samples were obtaine...
Western blot analysis of circulating apoA-IV. Serum samples were obtained at the conclusion of the 7-day experimental period, about 24 hours after the last intraperitoneal injection of rhA-IV. Serum samples were subjected to SDS-PAGE on 10% gels, transferred to nitrocellulose, then probed using an affinity-purified rabbit anti–rhA-IV antibody, followed by HRP-coupled goat anti-rabbit IgG antibody. (A) Effect of rhA-IV injection on serum apoA-IV in C57BL/6 mice from series I experiments. (B) Serum apoA-IV in an ApoA-IV–/– mouse with or without exogenous administration of rhA-IV, compared with serum apoA-IV in a WT littermate.
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