Estrogen and raloxifene inhibit the monocytic chemoattractant protein-1-induced migration of human monocytic cells via nongenomic estrogen receptor alpha
Yada-Hashimoto, N.; Nishio, Y.; Ohmichi, M.; Hayakawa, J.; Mabuchi, S.; Hisamoto, K.; Nakatsuji, Y.; Sasaki, H.; Seino-Noda, H.; Sakata, M.; Tasaka, K.; Murata, Y.
Menopause 13(6): 935-941
To investigate the effects of estradiol (E2) and raloxifene on the migration of human monocytic THP-1 cells to endothelium. A prospective comparative study. THP-1 cells, a human acute monocytic leukemia cell line, were used for the study. Migration assays were performed using transwell inserts. THP-1 cells were exposed to E2 or raloxifene in the presence of monocytic chemoattractant protein-1 (MCP-1), a major chemoattractant for monocytes. The cells were transfected with small interfering RNA (siRNA) against estrogen receptor (ER) alpha and ERbeta for gene silencing. ER expression was evaluated by Western blot analysis. MCP-1 induced the migration of the cells for 90 minutes. The addition of E2 or raloxifene significantly inhibited the MCP-1-induced migration for 90 minutes. Preincubation of THP-1 cells with an ER antagonist, ICI 182780, significantly attenuated the inhibitory effects of E2 and raloxifene. Whereas transfection with siRNA of ERalpha significantly attenuated the inhibition by E2 of MCP-1-induced monocyte migration, transfection with control siRNA or siRNA of ERbeta had no effect on the rapid inhibitory action of E2. Moreover, preincubation of THP-1 cells with a transcriptional inhibitor, actinomycin D, had no effect on the rapid inhibitory action of E2. Our findings suggest that both E2 and raloxifene inhibited the MCP-1-induced monocyte migration through nongenomic ERalpha. This result may explain one of the antiatherosclerotic effects of E2 and raloxifene on vasculature.