title: Butyrate inhibits leukocyte adhesion to endothelial cells via modulation of VCAM-1.
abstract: BACKGROUND
  Leukocyte recruitment to areas of inflammation depends on Integrin-VCAM/ICAM interaction. Blocking the vascular cell adhesion molecule (VCAM-1) and the intracellular adhesion molecule (ICAM-1) may have therapeutic benefit for the inflammatory component of bowel disease. Notably, the induction of ICAM and VCAM is mediated by a nuclear factor kappaB (NF-kappaB)-dependent mechanism. We investigated whether the anti-inflammatory properties of butyrate are mediated via the modulation of VCAM and ICAM on human endothelial cells.
  
  
  METHODS
  VCAM-1 and ICAM-1 expression on human endothelial cells upon tumor necrosis factor-alpha (TNF-alpha) stimulation was assessd by FACS analysis. A monocyte adhesion assay was performed to evaluate the relevance of a modulated CAM-expression. Electrophoretic mobility shift assays were applied to investigate NF-kappaB activation.
  
  
  RESULTS
  The observed butyrate-associated inhibition of monocyte adhesion to endothelial cells is associated with an inhibition of NF-kappaB activation in human endothelial cells. In this context, the observed suppression of the TNF-alpha induced VCAM-1 expression is likely to play an essential role.
  
  
  CONCLUSIONS
  Butyrate inhibits VCAM-1 mediated leukocyte adhesion to human endothelial cells. This inhibition may contribute to the anti-inflammatory effects of butyrate in patients with distal ulcerative colitis.
authors.affiliation: Division of Gastroenterology, Department of Medicine, University of Würzburg, Würzburg, Germany. menzel_t@medizin.uni-wuerzburg.de
authors.forename: Thomas
authors.initials: T
authors.lastname: Menzel
authors.forename: Hardi
authors.initials: H
authors.lastname: Lührs
authors.forename: Sabine
authors.initials: S
authors.lastname: Zirlik
authors.forename: Jürgen
authors.initials: J
authors.lastname: Schauber
authors.forename: Theodor
authors.initials: T
authors.lastname: Kudlich
authors.forename: Tobias
authors.initials: T
authors.lastname: Gerke
authors.forename: Andrea
authors.initials: A
authors.lastname: Gostner
authors.forename: Manfred
authors.initials: M
authors.lastname: Neumann
authors.forename: Ralph
authors.initials: R
authors.lastname: Melcher
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Scheppach
mesh_terms: D002087:Butyrates / Q000494:pharmacology*; D002478:Cells, Cultured; D004347:Drug Interactions; D024202:Electrophoretic Mobility Shift Assay; D004730:Endothelium, Vascular / Q000166:cytology* / Q000187:drug effects; D005434:Flow Cytometry; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000096:biosynthesis* / Q000187:drug effects; D012680:Sensitivity and Specificity; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*; D019010:Vascular Cell Adhesion Molecule-1 / Q000096:biosynthesis* / Q000187:drug effects
chemical_list: D002087:Butyrates; D014409:Tumor Necrosis Factor-alpha; D019010:Vascular Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1