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Novel Selective Estrogen Receptor Modulator Ameliorates Murine Colitis
- Source :
- International Journal of Molecular Sciences, Volume 20, Issue 12, International Journal of Molecular Sciences, Vol 20, Iss 12, p 3007 (2019)
- Publication Year :
- 2019
- Publisher :
- Multidisciplinary Digital Publishing Institute, 2019.
-
Abstract
- Estrogen-receptor-mediated signaling has been suggested to decrease the inflammatory response in monocyte macrophages. Previously, we showed that a novel selective estrogen receptor modulator (SERM2) promotes anti-inflammatory phenotype of monocytes in vitro. In this study, we demonstrate the potential of SERM2 in amelioration of colitis. We utilized a dextran sodium sulfate (DSS)-induced colitis model in FVB/n mice to demonstrate the effects of orally administered SERM2 on the clinical status of the mice and the histopathological changes in the colon, as well as proportion of Mrc-1 positive macrophages. SERM2 nuclear receptor affinities were measured by radioligand binding assays. Orally administered, this compound significantly alleviated DSS-induced colitis in male mice and induced local estrogen receptor activation in the inflamed colon, as well as promoting anti-inflammatory cytokine expression and infiltration of anti-inflammatory monocytes. We show that this novel drug candidate has an affinity to estrogen receptors &alpha<br />and &beta<br />and progesterone receptors, but not to glucocorticoid receptor, thus expressing unique binding properties compared to other sex steroid receptor ligands. These results indicate that novel drug candidates to alleviate inflammatory conditions of the colon could be found among sex steroid receptor activating compounds.
- Subjects :
- Male
Selective Estrogen Receptor Modulators
Colon
colitis
Dextran Sulfate
selective estrogen receptor modulator
Article
Monocytes
progesterone receptor
macrophages
lcsh:Chemistry
Disease Models, Animal
Mice
lcsh:Biology (General)
lcsh:QD1-999
inflammation
Animals
Cytokines
lcsh:QH301-705.5
estrogen receptor
Subjects
Details
- Language :
- English
- ISSN :
- 14220067
- Database :
- OpenAIRE
- Journal :
- International Journal of Molecular Sciences
- Accession number :
- edsair.pmid.dedup....03432fd9d7ce8b8faf3b4fc5fd85465c
- Full Text :
- https://doi.org/10.3390/ijms20123007