title: Inhibition of macrophage adhesion activity by 9trans,11trans-conjugated linoleic acid.
abstract: Conjugated linoleic acids (CLAs) have anti-atherogenic effects in both in vitro and animal models. Most studies on CLAs were performed with either a CLA mixture or purified 9cis (Z),11trans (E)-CLA or 10E,12Z-CLA isomers. However, the 9E,11E isomer has superior anti-carcinogenic and anti-inflammatory effects compared with the more abundant CLAs. The 9E,11E-CLA isomer specifically increases interleukin-1 receptor antagonist (IL-1Ra), an important anti-inflammatory mediator that is associated with decreased risk of coronary heart disease. The purpose of this present study was to determine if 9E,11E-CLA affects markers of atherogenesis via regulation of IL-1Ra. In human umbilical vein endothelial cells (HUVECs), 9E,11E-CLA decreased such atherogenesis-related genes as intercellular adhesion molecule-1, vascular cell adhesion molecule-1, monocyte chemoattractant protein-1, E-selectin, P-selectin and C-C motif chemokine receptor-2. Treatment of RAW 264.7 cells with 9E,11E-CLA decreased their adhesion to HUVECs. This effect was reversed by inhibiting the phosphoinositide 3-kinase or mouse target of rapamycin pathways. IL-1Ra-deficient RAW 264.7 cells (siIL-1Ra RAW) bind more efficiently to HUVECs compared with the control stable cells (si-control RAW). In addition, HUVECs treated with siIL-1Ra RAW-conditioned media induce significantly higher levels of intercellular adhesion molecule-1, vascular cell adhesion molecule-1, monocyte chemoattractant protein-1 and E-selectin than HUVECs treated with si-control RAW-conditioned media. Taken together, the data show that 9E,11E-CLA decreases the atherogenesis-related genes in HUVECs and alters adhesion of macrophages. In addition, the induction of IL-1Ra by 9E,11E-CLA is partially responsible for the anti-atherogenic properties of this particular CLA isomer.
authors.affiliation: Integrative Biosciences, Huck Institutes of the Life Sciences, Pennsylvania State University, University Park, PA 16802, USA.
authors.forename: Yunkyoung
authors.initials: Y
authors.lastname: Lee
authors.forename: John P
authors.initials: JP
authors.lastname: Vanden Heuvel
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D002448:Cell Adhesion; D016207:Cytokines / Q000378:metabolism; D042783:Endothelial Cells / Q000166:cytology; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D053590:Interleukin 1 Receptor Antagonist Protein / Q000378:metabolism; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism; D044243:Linoleic Acids, Conjugated / Q000494:pharmacology*; D008264:Macrophages / Q000187:drug effects* / Q000378:metabolism; D051379:Mice; D008954:Models, Biological; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D058570:TOR Serine-Threonine Kinases; D014471:Umbilical Veins / Q000166:cytology
chemical_list: D000893:Anti-Inflammatory Agents; D016207:Cytokines; D018799:Intercellular Adhesion Molecule-1; D053590:Interleukin 1 Receptor Antagonist Protein; D047908:Intracellular Signaling Peptides and Proteins; D044243:Linoleic Acids, Conjugated; D019869:Phosphatidylinositol 3-Kinases; D017346:Protein Serine-Threonine Kinases; D058570:TOR Serine-Threonine Kinases; C046938:9,11-linoleic acid; C546842:MTOR protein, human; C546843:mTOR protein, mouse