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

The expression of cell adhesion molecules on vascular smooth muscle cells is central to leukocyte re- 23 cruitment and progression of atherosclerotic disease. Ohioensin F, a chemical compound of the Antarctic 24 moss Polytrichastrum alpinum, exhibited inhibitory activity against protein tyrosine phosphatase 1B and an- 25 tioxidant activity. However, published scientific information regarding other biological activities and phar- 26 macological function of ohioensin F is scarce. In the present study, we aimed to examine the in vitro 27 effects of ohioensin F on the ability to suppress TNF-α-induced adhesion molecule expression in vascular 28 smooth muscle cells (VSMCs). 29 Main methods: The inhibitory effect of ohioensin F on TNF-α-induced upregulation in expression of adhesion 30 molecules was investigated by enzyme-linked immunosorbent assay, cell adhesion assay, RT- PCR, western 31 blot analysis, immunofluorescence, and transfection and reporter assay, respectively. 32 Key findings: Pretreatment of VSMCs with ohioensin F at nontoxic concentrations of 0.1？10 μg/ml dose- 33 dependently inhibited TNF-α-induced expression of vascular cell adhesion molecule-1 (VCAM-1) and inter- 34 cellular adhesion molecule-1 (ICAM-1). In addition, ohioensin F suppressed adhesion of THP-1 monocytes to 35 TNF-α-stimulated VSMCs. Ohioensin F reduced TNF-α-induced production of intracellular lpinum, exhibited inhibitory activity against protein tyrosine phosphatase 1B and an- 25 tioxidant activity. However, published scientific information regarding other biological activities and phar- 26 macological function of ohioensin F is scarce. In the present study, we aimed to examine the in vitro 27 effects of ohioensin F on the ability to suppress TNF-α-induced adhesion molecule expression in vascular 28 smooth muscle cells (VSMCs). 29 Main methods: The inhibitory effect of ohioensin F on TNF-α-induced upregulation in expression