School of Pharmacy, Sungkyunkwan University, Suwon, Kyunggi-do, 440-746, Republic of Korea.
Life Sci. 2012 Mar 10;90(11-12):396-406. doi: 10.1016/j.lfs.2011.12.017. Epub 2012 Jan 18.
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).
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.
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.
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.
细胞黏附分子在血管平滑肌细胞中的表达是白细胞募集和动脉粥样硬化疾病进展的核心。俄亥俄芬 F 是南极苔藓 Polyerichastrum alpinum 的一种化合物，具有抑制蛋白酪氨酸磷酸酶 1B 和抗氧化活性。然而，关于俄亥俄芬 F 的其他生物学活性和药理学功能的已发表科学信息却很少。在本研究中，我们旨在研究俄亥俄芬 F 对抑制血管平滑肌细胞 (VSMC) 中 TNF-α 诱导的黏附分子表达能力的体外作用。
通过酶联免疫吸附试验、细胞黏附试验、RT-PCR、western blot 分析、免疫荧光和转染及报告基因试验，分别研究了俄亥俄芬 F 对 TNF-α诱导的黏附分子表达上调的抑制作用。
俄亥俄芬 F 在非毒性浓度 0.1-10μg/ml 时预处理 VSMC，可剂量依赖性地抑制 TNF-α诱导的血管细胞黏附分子-1 (VCAM-1) 和细胞间黏附分子-1 (ICAM-1) 的表达。此外，俄亥俄芬 F 抑制了 THP-1 单核细胞与 TNF-α 刺激的 VSMC 的黏附。俄亥俄芬 F 减少了 TNF-α 诱导的细胞内活性氧 (ROS) 产生和 p38、ERK、JNK 和 Akt 的磷酸化。最后，俄亥俄芬 F 抑制了 TNF-α诱导的 CAM mRNA 表达和 NK-κB 易位。
这些结果表明，俄亥俄芬 F 的抗炎作用具有新的机制，这归因于其对血管平滑肌细胞中 TNF-α 诱导的黏附分子表达、单核细胞黏附和 ROS 产生的负调控。我们的发现还支持俄亥俄芬 F 作为一种潜在的具有抗炎作用的药理学分子，对动脉粥样硬化病变具有保护作用。
