A1 Vertaisarvioitu alkuperäisartikkeli tieteellisessä lehdessä
Novel Selective Estrogen Receptor Modulator Ameliorates Murine Colitis
Tekijät: Polari L, Anttila S, Helenius T, Wiklund A, Linnanen T, Toivola DM, Määttä J
Kustantaja: MDPI
Julkaisuvuosi: 2019
Journal: International Journal of Molecular Sciences
Tietokannassa oleva lehden nimi: INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
Lehden akronyymi: INT J MOL SCI
Artikkelin numero: ARTN 3007
Vuosikerta: 20
Numero: 12
Sivujen määrä: 14
ISSN: 1422-0067
eISSN: 1422-0067
DOI: https://doi.org/10.3390/ijms20123007
Verkko-osoite: 10.3390/ijms20123007
Rinnakkaistallenteen osoite: https://research.utu.fi/converis/portal/detail/Publication/41737986
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 and beta 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.
Ladattava julkaisu This is an electronic reprint of the original article. |  |
