Apolipoprotein A-IV inhibits experimental colitis

Thorsten Vowinkel

Mikiji Mori

Christian Krieglstein

Janice Russell

Patrick Tso+2 authors

^{Department of Molecular and Cellular Physiology, Louisiana State University Health Sciences Center, Shreveport, Louisiana, USA.}^{Department of General Surgery, Westfälische Wilhelms-Universität Münster, Munster, Germany.}^{Department of Surgery and}^{Department of Pediatrics, Louisiana State University Health Sciences Center, Shreveport, Louisiana, USA.}^{Department of Pathology and Laboratory Medicine, College of Medicine, University of Cincinnati, Cincinnati, Ohio, USA.}

Address correspondence to: Theodore J. Kalogeris, Department of Surgery, Louisiana State University Health Sciences Center, 1501 Kings Highway, Shreveport, Louisiana 71130-3932, USA. Phone: (318) 675-4354; Fax: (318) 675-6005; E-mail: ude.cshusl@golakt.

Received 2004 Feb 3; Accepted 2004 May 25.

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.

Abstract

Acknowledgments

The authors are grateful to Fu Qin Duan, William Goodwill, and Heather Spaulding for technical assistance. We also thank Nicholas Duverger for generously providing us with the pL2102-hA-IV plasmid. This study was supported by grants from the Deutsche Forschungsgemeinschaft, Bonn, Germany (VO 998/1-1 to T. Vowinkel), the NIH (P01 DK-43785 to D.N. Granger and R29 DK-52148 to T.J. Kalogeris), and by funds from the Department of Surgery at Louisiana State University Health Sciences Center.

Acknowledgments

Footnotes

Nonstandard abbreviations used: charge-coupled device (CCD); dextran sulfate sodium (DSS); disease activity index (DAI); inflammatory bowel disease (IBD); myeloperoxidase (MPO); recombinant human apoA-I (rhA-I); recombinant human apoA-IV (rhA-IV).

Conflict of interest: The authors have declared that no conflict of interest exists.

Footnotes

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