We have previously shown that 17β-estradiol (E2) 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 E2 action in the RAW 264.7 macrophage cell line. We show here that these cells express the α-isoform of the estrogen receptor (ERα) and not ERβ. Similarly to its activity in brain macrophages, E2 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 ERα 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.
|Number of pages||8|
|Journal||Journal of Steroid Biochemistry and Molecular Biology|
|Publication status||Published - Jun 2004|
- Estrogen receptor-alpha
- RAW cells
ASJC Scopus subject areas