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Selective estrogen receptor modulators regulate IL‐6 inflammatory response in ARPE‐19 cells
Author(s) -
PAIMELA T,
RYHÄNEN T,
VIIRI J,
HYTTINEN J,
UNKILA M,
UUSITALO HMT,
SALMINEN A,
KAARNIRANTA K
Publication year - 2008
Publication title -
acta ophthalmologica
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.534
H-Index - 87
eISSN - 1755-3768
pISSN - 1755-375X
DOI - 10.1111/j.1755-3768.2008.410.x
Subject(s) - selective estrogen receptor modulator , estrogen receptor , estrogen , estrogen receptor beta , innate immune system , transfection , retinal pigment epithelium , pharmacology , biology , receptor , chemistry , microbiology and biotechnology , endocrinology , medicine , retinal , cell culture , biochemistry , genetics , cancer , breast cancer
Purpose Recent findings reveal that Toll‐like receptors (TLRs) and innate immunity participate in the pathology of age‐related macular degeneration (AMD). Many studies indicate that estrogens and selective estrogen modulators (SERMs) modulate inflammatory responses, but their effect on the development of AMD is weakly understood. In this study, we investigated the regulatory role of various SERMs (provided by Hormos Medical Ltd.) on IL‐6 expression in human retinal pigment epithelial cells (ARPE‐19). Methods ARPE‐19 cells were exposed to lipopolysaccharide (LPS; TLR 4 agonist) with simultaneous exposure to various SERMs and the secretion of IL‐6 cytokine was analyzed by ELISA. The estrogen receptor alpha and beta were qualitatively measured by RT‐PCR. To study the effect of various SERM treatments of estrogen response element (ERE) ‐mediated transcription, the ARPE‐19 cells were transiently transfected with ERE‐luciferase vector. The activity of ERE was measured by Luciferase assay. Results Simultaneous exposures to LPS and SERM‐320 reduced the IL‐6 expression levels in ARPE‐19 cells compared to LPS exposure alone. The RT‐PCR analysis showed that ARPE‐19 cells expressed estrogen receptor alpha but not beta proteins. Interestingly, SERM‐320 did not increase the activity of ERE in ARPE cells. This reveals that SERM‐320 is implicated in regulation of IL‐6 expression, but is not mediated through estrogen response element. Conclusion Our findings reveal that SERM‐320 is a novel compound to suppress innate immunity response in human retinal pigment epithelial cells.