Inhibitory effect of trans-caryophyllene (TC) on leukocyte-endothelial attachment

Toxicol Appl Pharmacol. 2017 Aug 15;329:326-333. doi: 10.1016/j.taap.2017.06.016. Epub 2017 Jun 15.

Abstract

trans-Caryophyllene (TC) is a major component found in the essential oils of many spices and foods/medicinal plants. It is a natural sesquiterpene and has been the subject of numerous studies. However, the effects of TC on vascular inflammation remain unknown. In this study, we reported that TC treatment in human umbilical vein endothelial cells (HUVECs) prevented attachment of monocytic leukemia cell line THP-1 cells to endothelial cells. In addition, in vivo results indicate that TC inhibited macrophage infiltration to the aortic surface and reduced total serum levels of cholesterol and triglycerides. Importantly, administration of TC could inhibit the induction of vascular cell adhesion molecule-1 (VCAM-1) both in vitro and in vivo. Notably, our data indicate that the inhibitory effects of TC on the expression of VCAM-1 are mediated by the JAK2/STAT1/IRF-1 pathway. TC is a specific agonist of the type 2 cannabinoid receptor (CB2R). Importantly, we further verified that the inhibitory effects of TC on the expression of IRF-1 and VCAM-1 are dependent on activation of CB2R. Inhibition of CB2R by either specific inhibitors or RNA interference abolished the inhibitory effects of TC on the expression of IRF-1 and VCAM-1. Our results suggest that TC might have a capacity to suppress the development of atherosclerosis.

Keywords: IFN regulatory factor-1 (IRF-1); Type 2 cannabinoid receptor (CB2R); Vascular cell adhesion molecule-1 (VCAM-1); Vascular inflammation; trans-Caryophyllene.

MeSH terms

  • Animals
  • Anti-Inflammatory Agents / pharmacology*
  • Aorta / drug effects*
  • Aorta / metabolism
  • Aorta / pathology
  • Aortic Diseases / blood
  • Aortic Diseases / genetics
  • Aortic Diseases / pathology
  • Aortic Diseases / prevention & control*
  • Atherosclerosis / blood
  • Atherosclerosis / genetics
  • Atherosclerosis / pathology
  • Atherosclerosis / prevention & control*
  • Cell Adhesion / drug effects*
  • Cell Line
  • Cholesterol / blood
  • Coculture Techniques
  • Disease Models, Animal
  • Dose-Response Relationship, Drug
  • Human Umbilical Vein Endothelial Cells / drug effects*
  • Human Umbilical Vein Endothelial Cells / metabolism
  • Human Umbilical Vein Endothelial Cells / pathology
  • Humans
  • Intercellular Adhesion Molecule-1 / genetics
  • Intercellular Adhesion Molecule-1 / metabolism
  • Interferon Regulatory Factor-1 / genetics
  • Interferon Regulatory Factor-1 / metabolism
  • Janus Kinase 2 / genetics
  • Janus Kinase 2 / metabolism
  • Leukocytes / drug effects*
  • Leukocytes / metabolism
  • Leukocytes / pathology
  • Macrophages / drug effects
  • Macrophages / metabolism
  • Macrophages / pathology
  • Male
  • Mice, Inbred C57BL
  • Plaque, Atherosclerotic
  • Polycyclic Sesquiterpenes
  • RNA Interference
  • Receptor, Cannabinoid, CB2 / genetics
  • Receptor, Cannabinoid, CB2 / metabolism
  • STAT1 Transcription Factor / genetics
  • STAT1 Transcription Factor / metabolism
  • Sesquiterpenes / pharmacology*
  • Signal Transduction / drug effects
  • Transendothelial and Transepithelial Migration / drug effects*
  • Transfection
  • Triglycerides / blood
  • Vascular Cell Adhesion Molecule-1 / genetics
  • Vascular Cell Adhesion Molecule-1 / metabolism

Substances

  • Anti-Inflammatory Agents
  • CNR2 protein, human
  • ICAM1 protein, human
  • IRF1 protein, human
  • Interferon Regulatory Factor-1
  • Polycyclic Sesquiterpenes
  • Receptor, Cannabinoid, CB2
  • STAT1 Transcription Factor
  • STAT1 protein, human
  • Sesquiterpenes
  • Triglycerides
  • Vascular Cell Adhesion Molecule-1
  • Intercellular Adhesion Molecule-1
  • Cholesterol
  • caryophyllene
  • JAK2 protein, human
  • Janus Kinase 2