Abstract 20023: ApoA-I Mimetic Peptide 4F Inhibits Inflammatory Bowel Disease in Mice
Introduction: Inflammatory bowel disease (IBD) has been linked to an increased prevalence of early stage vascular disease. The apoA-I mimetic peptide 4F is a potential therapeutic agent for the treatment of inflammatory diseases including atherosclerosis. The mechanism of action of 4F is localized to the small intestine, where we have shown that 4F can alter lipid signaling and regulate cholesterol efflux.
Hypothesis: Given the mechanism of action, we hypothesized that 4F might protect against the development of IBD. We previously reported that COX-2 deficient mice develop Crohn’s-like disease when fed a cholate diet. We thus examined whether 4F treatment alters the development of Crohn’s-like inflammation in this IBD model.
Methods: Myeloid COX-2 deficient mice were challenged with a cholate-containing diet while being treated with 4F. After 7 and 10 weeks, the surviving mice were sacrificed and analyzed for intestinal inflammation in the ileo-ceco-colic junction by gross histology and immunohistochemistry (IHC). Total cecal RNA was analyzed for inflammatory cytokines.
Results: Only 57% (8/14) of control mice, but all 4F-treated mice (14/14) survived. 4F significantly reduced by 50% the thickness of the ileo-ceco-colic junctions while reducing muscularis thickness 5-fold. By 7 weeks, 4F treatment significantly inhibited TNFα while significantly increasing IL-10. 4F also significantly reduced the number of infiltrating macrophages (F4/80) and neutrophils (Ly6G) by 3 and 5-fold as measured by IHC.
Conclusions: 4F treatment largely abrogated measures of IBD in a COX2-deficient mouse model of Crohn’s disease.
Author Disclosures: D. Meriwether: None. C. Volpe: None. V. Grijalva: None. P. Mukherjee: None. M. Martin: None. G. Anantharamaiah: Other; Significant; Principal, Bruin Pharma. A.M. Fogelman: Other; Significant; Officer and Principal, Bruin Pharma. S.T. Reddy: Other; Significant; Principal, Bruin Pharma.
- © 2016 by American Heart Association, Inc.