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  • Title: Influence of selective estrogen receptor modulators on interleukin-6 expression in human retinal pigment epithelial cells (ARPE-19).
    Author: Paimela T, Hyttinen JM, Viiri J, Ryhänen T, Karvonen MK, Unkila M, Uusitalo H, Salminen A, Kaarniranta K.
    Journal: Eur J Pharmacol; 2010 Aug 25; 640(1-3):219-25. PubMed ID: 20546720.
    Abstract:
    Since estrogen and selective estrogen receptor modulators can inhibit inflammatory responses, we studied the regulatory role of several selective estrogen receptor modulators on interleukin-6 (IL-6) expression in human retinal pigment epithelial cells (ARPE-19). ARPE-19 cells were exposed to lipopolysaccharide with simultaneous exposure to different selective estrogen receptor modulators with the secretion of IL-6 cytokine being analyzed by enzyme-linked immunosorbent assay (ELISA). We demonstrate that 17beta-estradiol and HM-D, a novel selective estrogen receptor modulator compound, clearly reduced the IL-6 expression levels after lipopolysaccharide exposure in ARPE-19 cells. Molecular effects of selective estrogen receptor modulators and estrogen on the estrogen response element-mediated transcription were studied using MCF-7 and ARPE-19 cell lines carrying the estrogen response element-luciferase reporter gene. Estrogen and HM-D stimulated the activity of estrogen response element-reporter gene in MCF-7 cells but did not affect the activity in ARPE-19 cells. In addition, HM-D did not activate estrogen receptor alpha when studied by nuclear receptor peptide estrogen receptor alpha ELISA in ARPE-19 cells. These results indicate that estrogen and HM-D can suppress the lipopolysaccharide-induced inflammatory response but signalling is not mediated through estrogen response element transcription in human retinal pigment epithelial cells.
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