Butter feeding enhances TNF-alpha production from macrophages and lymphocyte adherence in murine small intestinal microvessels.
OBJECTIVE
Dietary fat is known to modulate immune functions. Intake of an animal fat-rich diet has been linked to increased risk of inflammation; however, little is known about how animal fat ingestion directly affects intestinal immune function. The objective of this study was to assess the effect of butter feeding on lymphocyte migration in intestinal mucosa and the changes in adhesion molecules and cytokines involved in this effect.


METHODS
T-lymphocytes isolated from the spleen were fluorescence-labeled and injected into recipient mice. Butter was administered into the duodenum, and villus microvessels of the small intestinal mucosa were observed under an intravital microscope. mRNA expression of adhesion molecules and cytokines in the intestinal mucosa were determined by quantitative PCR. The effect of butter feeding on tumor necrosis factor (TNF)-alpha mRNA expression of intestinal macrophages was also determined.


RESULTS
Intraluminal butter administration significantly increased lymphocyte adherence to intestinal microvessels accompanied by increases in expression levels of adhesion molecules ICAM-1, MAdCAM-1 and VCAM-1. This accumulation was significantly attenuated by anti-MAdCAM-1 and anti-ICAM-1 antibodies. Butter administration significantly increased TNF-alpha in the lamina proprial macrophages but not interleukin-6. Anti-TNF-alpha treatment attenuated the enhanced expression of adhesion molecules induced by butter administration.


CONCLUSIONS
T-lymphocyte adherence to microvessels of the small intestinal mucosa was significantly enhanced after butter ingestion. This enhancement is due to increase in expression levels of adhesion molecules of the intestinal mucosa, which is mediated by TNF-alpha from macrophages in the intestinal lamina propria.
Fujiyama
Yoichi
Y
Department of Internal Medicine, School of Medicine, Keio University, Tokyo, Japan.
Hokari
Ryota
R
Miura
Soichiro
S
Watanabe
Chikako
C
Komoto
Shunsuke
S
Oyama
Tokushige
T
Kurihara
Chie
C
Nagata
Hiroshi
H
Hibi
Toshifumi
T
D000818:Animals; D000906:Antibodies; D002079:Butter; D002448:Cell Adhesion / Q000187:drug effects*; D015815:Cell Adhesion Molecules / Q000276:immunology / Q000378:metabolism; D002634:Chemotaxis, Leukocyte / Q000187:drug effects*; D004041:Dietary Fats / Q000008:administration & dosage / Q000494:pharmacology*; D005260:Female; D007150:Immunohistochemistry; D018799:Intercellular Adhesion Molecule-1 / Q000276:immunology / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D007413:Intestinal Mucosa / Q000098:blood supply / Q000187:drug effects* / Q000378:metabolism; D007441:Intubation, Gastrointestinal; D019787:Linoleic Acid / Q000494:pharmacology; D008264:Macrophages / Q000187:drug effects* / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008833:Microcirculation / Q000187:drug effects; D018715:Microscopy, Video; D008871:Microvilli / Q000187:drug effects / Q000378:metabolism; D009088:Mucoproteins; D019301:Oleic Acid / Q000494:pharmacology; D000069463:Olive Oil; D010938:Plant Oils / Q000494:pharmacology; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000378:metabolism; D013601:T-Lymphocytes / Q000187:drug effects* / Q000378:metabolism; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism*; D015854:Up-Regulation; D019010:Vascular Cell Adhesion Molecule-1 / Q000276:immunology / Q000378:metabolism
D000906:Antibodies; D015815:Cell Adhesion Molecules; D004041:Dietary Fats; D015850:Interleukin-6; C489082:Madcam1 protein, mouse; D009088:Mucoproteins; D000069463:Olive Oil; D010938:Plant Oils; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D019010:Vascular Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1; D019301:Oleic Acid; D002079:Butter; D019787:Linoleic Acid