title: High levels of fish oil enhance neutrophil development and activation and influence colon mucus barrier function in a genetically susceptible mouse model.
abstract: Dietary fatty acids influence immunologic homeostasis, but their effect on initiation of colitis, an immune-mediated disease, is not well established. Previously, our laboratory demonstrated that high doses of dietary fish oil (FO) increased colon inflammation and dysplasia in a model of infection-induced colitis. In the current study, we assessed the effects of high-dose dietary FO, 6% by weight, on colon inflammation, neutrophil recruitment and function, and mucus layer integrity in a genetically susceptible, colitis-prone mouse model in the absence of infection. FO-fed SMAD3(-/-) mice had increased colon inflammation evidenced by increased numbers of systemic and local neutrophils and increased neutrophil chemoattractant and inflammatory cytokine gene expression in the colon. Mucus layer thickness in the cecum and goblet cell numbers in the cecum and colon in FO-fed mice were reduced compared to control. FO consumption affected colitis in male and female mice differently. Compared to female control mice, neutrophils from FO-fed female mice had reduced reactive oxygen species (ROS) upon ex vivo stimulation with phorbol myristate acetate while FO-fed male mice produced increased ROS compared to control-fed male mice. In summary, dietary FO impaired mucus layer integrity and was associated with colon inflammation characterized by increased neutrophil numbers and altered neutrophil function. High-dose FO may have detrimental effects in populations genetically susceptible for inflammatory bowel disease and these effects may differ between males and females.
authors: Department of Food Science & Human Nutrition, Michigan State University East Lansing, MI, 48824.
authors: David M
authors: DM
authors: Duriancik
authors: Department of Food Science & Human Nutrition, Michigan State University East Lansing, MI, 48824.
authors: Sarah S
authors: SS
authors: Comstock
authors: Department of Pathobiological Sciences Louisiana State University, Baton Rouge, LA, 70803.
authors: Ingeborg M
authors: IM
authors: Langohr
authors: Department of Food Science & Human Nutrition, Michigan State University East Lansing, MI, 48824. Electronic address: imigjeni@anr.msu.edu.
authors: Jenifer I
authors: JI
authors: Fenton
mesh_terms: D000818:Animals; D001854:Bone Marrow Cells / Q000187:drug effects; D003092:Colitis / Q000139:chemically induced* / Q000473:pathology; D003106:Colon / Q000187:drug effects*; D005260:Female; D005395:Fish Oils / Q000009:adverse effects / Q000494:pharmacology*; D005786:Gene Expression Regulation / Q000187:drug effects; D007413:Intestinal Mucosa / Q000187:drug effects / Q000473:pathology; D008297:Male; D008817:Mice, Mutant Strains; D009504:Neutrophils / Q000187:drug effects*; D051900:Smad3 Protein / Q000235:genetics
chemical_list: D005395:Fish Oils; D051900:Smad3 Protein; C497791:Smad3 protein, mouse
keywords: B lymphocyte; Colon; Fish oil; Inflammation; Mucosal barrier; Neutrophil