17β-Oestradiol Anti-Inflammatory Effects in Primary Astrocytes Require Oestrogen Receptor β-Mediated Neuroglobin Up-Regulation.

Neuroglobin (Ngb), so named after its initial discovery in brain neurones, has received great attention as a result of 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 effects against H₂O₂ toxicity. The involvement of Ngb in other brain cell populations, as well as in other neuroprotective effects of E₂, is completely unknown at present. We demonstrate Ngb immunoreactivity in reactive astrocytes located in the proximity of a penetrating cortical injury in vivo and the involvement of Ngb in the E₂-mediated anti-inflammatory effect in primary cortical astrocytes. Upon binding to oestrogen receptor ( ER)β, 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 demonstrated. 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 for mediating 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). Ngb can be regarded as a key mediator of the different protective effects of E₂ in the brain, including protection against oxidative stress and the control of inflammation, both of which are at the root of several neurodegenerative diseases. [ABSTRACT FROM AUTHOR]