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

E. De Marinis, E. Acaz-Fonseca, M. A. Arevalo, P. Ascenzi, M. Fiocchetti, M. Marino, L. M. Garcia-Segura

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish
Pages (from-to)260-270
Number of pages11
JournalJournal of Neuroendocrinology
Volume25
Issue number3
DOIs
Publication statusPublished - Mar 2013

Keywords

  • Astrocytes
  • Neuroglobin
  • Neuroinflammation
  • Oestrogen receptor

ASJC Scopus subject areas

  • Endocrinology
  • Endocrinology, Diabetes and Metabolism
  • Endocrine and Autonomic Systems
  • Cellular and Molecular Neuroscience

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