17β-Oestradiol anti-inflammatory effects in primary astrocytes require oestrogen receptor β-mediated neuroglobin up-regulation.

Abstract Neuroglobin (Ngb), so named after its initial discovery in brain neurones, received great attention due to its neuroprotective effects both in vitro and in vivo. Recently, we demonstrated that, in neurones, Ngb is a 17β-oestradiol (E2) inducible protein that is pivotal for hormone-induced anti-apoptotic effect against H(2) O(2) toxicity. The Ngb involvement in other brain cell populations as well as in other neuroprotective effects of E2 is nowadays completely unknown. Here we demonstrate Ngb immunoreactivity in reactive astrocytes located in proximity of a penetrating cortical injury in vivo and the involvement of Ngb in E2-mediated anti-inflammatory effect in primary cortical astrocytes. Upon binding to oestrogen receptor β (ERβ), E2 enhances Ngb levels in a dose-dependent manner. Although with a lesser degree than E2, the pro-inflammatory stimulation with lipopolysaccharide (LPS) also induces the increase of Ngb protein levels via Nuclear Factor- (NF)κB signal(s). Moreover, a negative cross-talk between ER subtypes and NFκB signal(s) has been evidenced. In particular, ERα-activated signals prevent the NFκB-mediated Ngb increase, whereas LPS impairs the ERβ-induced up-regulation of Ngb. Therefore, the co-expression of both ERα and ERβ is pivotal to mediate E2-induced Ngb expression in the presence of NFκB-activated signals. Interestingly, Ngb silencing prevents the effect of E2 on the expression of inflammatory markers (i.e., interleukin 6 and interferon γ-inducible protein 10). As a whole, Ngb can be regarded as a key mediator of different E2 protective effects in the brain that include protection against oxidative stress and control of inflammation, both of which are at the root of several neurodegenerative diseases. © 2012 British Society for Neuroendocrinology.