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The Journal of Neuroscience, March 15, 2001, 21(6):1809-1818
Estrogen Prevents the Lipopolysaccharide-Induced
Inflammatory Response in Microglia
Elisabetta
Vegeto1,
Cinzia
Bonincontro1,
Giuseppe
Pollio1,
Angelo
Sala2,
Serena
Viappiani2,
Francesca
Nardi2,
Alessia
Brusadelli1,
Barbara
Viviani2,
Paolo
Ciana1, and
Adriana
Maggi1
1 Milano Molecular Pharmacology Lab, and
2 Institute of Pharmacological Sciences, University of
Milan, 20133 Milan, Italy
After neuronal injury and in several neurodegenerative diseases,
activated microglia secrete proinflammatory molecules that can
contribute to the progressive neural damage. The recent demonstration of a protective role of estrogen in neurodegenerative disorders in
humans and experimental animal models led us to investigate whether
this hormone regulates the inflammatory response in the CNS. We here
show that estrogen exerts an anti-inflammatory activity on primary
cultures of rat microglia, as suggested by the blockage of the
phenotypic conversion associated with activation and by the prevention
of lipopolysaccharide-induced production of inflammatory mediators: inducible form of NO synthase (iNOS),
prostaglandin-E2 (PGE2), and
metalloproteinase-9 (MMP-9). These effects are dose-dependent, maximal
at 1 nM 17 -estradiol, and can be blocked by the estrogen receptor (ER) antagonist ICI 182,780. The demonstration of ER and
ER expression in microglia and macrophages and the observation of
estrogen blockade of MMP-9 mRNA accumulation and MMP-9 promoter induction further support the hypothesis of a genomic activity of
estrogen via intracellular receptors. This is the first report showing
an anti-inflammatory activity of estrogen in microglia. Our study
proposes a novel explanation for the protective effects of estrogen in
neurodegenerative and inflammatory diseases and provides new molecular
and cellular targets for the screening of ER ligands acting in the CNS.
Key words:
estrogen; microglia; macrophage; iNOS; PGE2; MMP-9
Copyright © 2001 Society for Neuroscience 0270-6474/01/2161809-10$05.00/0
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