Inhibition of cellular adhesion in human umbilical vein endothelial cells by NF-kappaB inhibitor DHMEQ under flow.
We previously designed and synthesized DHMEQ as an inhibitor of NF-kappaB. In the present study, we looked into the effect of DHMEQ on the cell adhesion in human umbilical vein endothelial cells (HUVEC) under flow. We used freshly prepared HUVEC and human mononuclear cells throughout the experiment. DHMEQ inhibited TNF-alpha-, IL-1beta-, and LPS-induced NF-kappaB activation in HUVEC. It also inhibited TNF-alpha-induced expression of intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), and E-selectin. DHMEQ also inhibited TNF-alpha-induced mononuclear cell-HUVEC adhesion. The effect of DHMEQ was more prominent when the cells were under shear stress. DHMEQ inhibited the adhesion between HUVEC and HT-29 colon cancer cells more clearly under the flow condition than under the static condition of the culture medium. These results suggest that DHMEQ, being a unique inhibitor of NF-kappaB, may be effective in suppressing atherosclerosis and metastasis by inhibiting the expression of adhesion molecules.
Ohno
Osamu
O
Department of Applied Chemistry, Faculty of Science and Technology, Keio University, 3-14-1 Hiyoshi, Kohoku-ku, Yokohama 223-0061, Japan.
Shima
Yutaka
Y
Ikeda
Yasuo
Y
Sakurai
Kumi
K
Watanabe
Kiyoaki
K
Kawai
Yohko
Y
Umezawa
Kazuo
K
D001549:Benzamides / Q000494:pharmacology*; D001696:Biomechanical Phenomena; D015153:Blotting, Western; D002448:Cell Adhesion / Q000187:drug effects; D018929:Cell Culture Techniques; D002478:Cells, Cultured; D003512:Cyclohexanones / Q000494:pharmacology*; D024202:Electrophoretic Mobility Shift Assay; D042783:Endothelial Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000096:biosynthesis; D007962:Leukocytes / Q000166:cytology; D016328:NF-kappa B / Q000037:antagonists & inhibitors*; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D014471:Umbilical Veins / Q000166:cytology