Influence of selective estrogen receptor modulators on interleukin-6 expression in human retinal pigment epithelial cells (ARPE-19).
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.
Paimela
Tuomas
T
Department of Ophthalmology, Institute of Clinical Medicine, University of Eastern Finland, and Kuopio University Hospital, P.O. Box 1627, FIN-70211 Kuopio, Finland.
Hyttinen
Juha M T
JM
Viiri
Johanna
J
Ryhänen
Tuomas
T
Karvonen
Matti K
MK
Unkila
Mikko
M
Uusitalo
Hannu
H
Salminen
Antero
A
Kaarniranta
Kai
K
D000475:Alkenes / Q000737:chemistry / Q000494:pharmacology; D000893:Anti-Inflammatory Agents / Q000378:metabolism / Q000494:pharmacology; D045744:Cell Line, Tumor; D004958:Estradiol / Q000494:pharmacology; D047628:Estrogen Receptor alpha / Q000235:genetics / Q000378:metabolism; D047629:Estrogen Receptor beta / Q000378:metabolism; D004967:Estrogens / Q000235:genetics; D005786:Gene Expression Regulation / Q000187:drug effects*; D006801:Humans; D015850:Interleukin-6 / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000494:pharmacology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011960:Receptors, Estrogen / Q000819:agonists / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D020218:Response Elements / Q000235:genetics; D055213:Retinal Pigment Epithelium / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism*; D013379:Substrate Specificity; D015533:Transcriptional Activation / Q000187:drug effects
D000475:Alkenes; D000893:Anti-Inflammatory Agents; D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; D004967:Estrogens; D015850:Interleukin-6; D008070:Lipopolysaccharides; D012333:RNA, Messenger; D011960:Receptors, Estrogen; D004958:Estradiol