title: Ohioensin F suppresses TNF-α-induced adhesion molecule expression by inactivation of the MAPK, Akt and NF-κB pathways in vascular smooth muscle cells.
abstract: OBJECTIVE
  The expression of cell adhesion molecules on vascular smooth muscle cells is central to leukocyte recruitment and progression of atherosclerotic disease. Ohioensin F, a chemical compound of the Antarctic moss Polyerichastrum alpinum, exhibited inhibitory activity against protein tyrosine phosphatase 1B and antioxidant activity. However, published scientific information regarding other biological activities and pharmacological function of ohioensin F is scarce. In the present study, we aimed to examine the in vitro effects of ohioensin F on the ability to suppress TNF-α-induced adhesion molecule expression in vascular smooth muscle cells (VSMCs).
  
  
  METHODS
  The inhibitory effect of ohioensin F on TNF-α-induced upregulation in expression of adhesion molecules was investigated by enzyme-linked immunosorbent assay, cell adhesion assay, RT-PCR, western blot analysis, immunofluorescence, and transfection and reporter assay, respectively.
  
  
  RESULTS
  Pretreatment of VSMCs with ohioensin F at nontoxic concentrations of 0.1-10 μg/ml dose-dependently inhibited TNF-α-induced expression of vascular cell adhesion molecule-1 (VCAM-1) and intercellular adhesion molecule-1 (ICAM-1). In addition, ohioensin F suppressed adhesion of THP-1 monocytes to TNF-α-stimulated VSMCs. Ohioensin F reduced TNF-α-induced production of intracellular reactive oxygen species (ROS) and phosphorylation of p38, ERK, JNK and Akt. Finally, ohioensin F inhibited TNF-α-induced CAM mRNA expression and NK-κB translocation.
  
  
  CONCLUSIONS
  These results suggest a new mechanism of ohioensin F's anti-inflammatory action, owing to the negative regulation of TNF-α-induced adhesion molecule expression, monocyte adhesion and ROS production in vascular smooth muscle cells. Our finding also supports ohioensin F as a potential pharmacological, anti-inflammatory molecule that has a protective effect on the atherosclerotic lesion.
authors.affiliation: School of Pharmacy, Sungkyunkwan University, Suwon, Kyunggi-do, 440-746, Republic of Korea.
authors.forename: Hye-Eun
authors.initials: HE
authors.lastname: Byeon
authors.forename: Sung Hee
authors.initials: SH
authors.lastname: Um
authors.forename: Joung Han
authors.initials: JH
authors.lastname: Yim
authors.forename: Hong Kum
authors.initials: HK
authors.lastname: Lee
authors.forename: Suhkneung
authors.initials: S
authors.lastname: Pyo
mesh_terms: D000818:Animals; D050197:Atherosclerosis / Q000378:metabolism*; D015153:Blotting, Western; D044002:Bryophyta / Q000737:chemistry*; D015815:Cell Adhesion Molecules / Q000378:metabolism*; D002460:Cell Line; D004305:Dose-Response Relationship, Drug; D004797:Enzyme-Linked Immunosorbent Assay; D005455:Fluorescent Antibody Technique; D006576:Heterocyclic Compounds, 4 or More Rings / Q000032:analysis / Q000737:chemistry / Q000494:pharmacology*; D066298:In Vitro Techniques; D051379:Mice; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D015394:Molecular Structure; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000378:metabolism*; D016328:NF-kappa B / Q000378:metabolism; D051058:Oncogene Protein v-akt / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000187:drug effects*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*; D014966:Xanthenes / Q000032:analysis / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D015815:Cell Adhesion Molecules; D006576:Heterocyclic Compounds, 4 or More Rings; D016328:NF-kappa B; D014409:Tumor Necrosis Factor-alpha; D014966:Xanthenes; C528982:ohioensin F; D051058:Oncogene Protein v-akt; D020928:Mitogen-Activated Protein Kinases