We have previously shown that 17beta-estradiol (E-2) prevents the activation of brain macrophages, i.e. microglia cells, both in vitro and in vivo. Hormone exerts this inhibitory effect by inhibiting pro-inflammatory gene expression. In this study we further investigated on the molecular mechanism of E-2 action in the RAW 264.7 macrophage cell line. We show here that these cells express the alpha-isoform of the estrogen receptor (ERalpha) and not ERbeta. Similarly to its activity in brain macrophages, E-2 is able to inhibit the activation program induced by lipopolysaccharide (LPS) in RAW 264.7 cells, as shown by the inhibitory effect of hormone on the morphological conversion and matrix metalloproteinase-9 (MMP-9) expression induced by the endotoxin. In addition, we demonstrate that hormone treatment is not associated with a reduction in the steady-state expression of Toll-like receptor-4 (TLR-4) and CD14, two components of the LPS receptor complex. Our results further confirm the anti-inflammatory role of ERalpha in macrophages and propose that the mechanism of hormone action on macrophage reactivity involves signaling molecules which are down-stream effectors of the LPS membrane receptors. (C) 2004 Elsevier Ltd. All rights reserved.

Regulation of the lipopolysaccharide signal transduction pathway by 17 beta-estradiol in macrophage cells / E. Vegeto, S. Ghisletti, C. Meda, S. Etteri, S. Belcredito, A. Maggi. - In: JOURNAL OF STEROID BIOCHEMISTRY AND MOLECULAR BIOLOGY. - ISSN 0960-0760. - 91:1-2(2004 Jun), pp. 59-66.

Regulation of the lipopolysaccharide signal transduction pathway by 17 beta-estradiol in macrophage cells

E. Vegeto
Primo
;
S. Ghisletti
Secondo
;
C. Meda;S. Etteri;S. Belcredito
Penultimo
;
A. Maggi
Ultimo
2004

Abstract

We have previously shown that 17beta-estradiol (E-2) prevents the activation of brain macrophages, i.e. microglia cells, both in vitro and in vivo. Hormone exerts this inhibitory effect by inhibiting pro-inflammatory gene expression. In this study we further investigated on the molecular mechanism of E-2 action in the RAW 264.7 macrophage cell line. We show here that these cells express the alpha-isoform of the estrogen receptor (ERalpha) and not ERbeta. Similarly to its activity in brain macrophages, E-2 is able to inhibit the activation program induced by lipopolysaccharide (LPS) in RAW 264.7 cells, as shown by the inhibitory effect of hormone on the morphological conversion and matrix metalloproteinase-9 (MMP-9) expression induced by the endotoxin. In addition, we demonstrate that hormone treatment is not associated with a reduction in the steady-state expression of Toll-like receptor-4 (TLR-4) and CD14, two components of the LPS receptor complex. Our results further confirm the anti-inflammatory role of ERalpha in macrophages and propose that the mechanism of hormone action on macrophage reactivity involves signaling molecules which are down-stream effectors of the LPS membrane receptors. (C) 2004 Elsevier Ltd. All rights reserved.
Estrogen receptor-alpha ; RAW cells ; Microglia ; MMP-9 ; TLR-4 ; CD14 ; Expression
Settore BIO/14 - Farmacologia
giu-2004
Article (author)
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2434/185929
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