Saijo K, Collier JG, Li AC, Katzenellenbogen JA, Glass CK.
An ADIOL-ERβ-CtBP transrepression pathway negatively regulates microglia-mediated inflammation.
Cell. 2011 May 13;145(4):584-95.
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Saijo et al. provide an interesting and thorough report of the anti-inflammatory effect of synthetic and endogenous estrogens via estrogen receptor β. The authors report that endogenous ADIOL selectively modulates ERβ and prevents development of experimental autoimmune encephalomyelitis (EAE) in mice. Importantly, ADIOL induces partial remission if administered after disease onset. The authors provide in vitro data to support a model that the ERβ-dependent modulation of inflammation occurs via astrocytes and microglia. However, the limitation of these cell culture conditions—growth in serum, cell purity (see Cahoy et al., 2008), emphasizes the importance of cell type-specific manipulation of ERβ in vivo to discern the relative contribution of CNS, such as oligodendrocytes (see Zhang et al., 2004) and immune cell types to ADIOL’s anti-inflammatory effects.
Cahoy JD, Emery B, Kaushal A, Foo LC, Zamanian JL, Christopherson KS, Xing Y, Lubischer JL, Krieg PA, Krupenko SA, Thompson WJ, Barres BA.
A transcriptome database for astrocytes, neurons, and oligodendrocytes: a new resource for understanding brain development and function.
J Neurosci. 2008 Jan 2;28(1):264-78.
Zhang Z, Cerghet M, Mullins C, Williamson M, Bessert D, Skoff R.
Comparison of in vivo and in vitro subcellular localization of estrogen receptors alpha and beta in oligodendrocytes.
J Neurochem. 2004 May;89(3):674-84.