PMID- 15261308 OWN - NLM STAT- MEDLINE DCOM- 20040914 LR - 20220227 IS - 0960-0760 (Print) IS - 0960-0760 (Linking) VI - 91 IP - 1-2 DP - 2004 Jun TI - Regulation of the lipopolysaccharide signal transduction pathway by 17beta-estradiol in macrophage cells. PG - 59-66 AB - We have previously shown that 17beta-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 alpha-isoform of the estrogen receptor (ERalpha) and not ERbeta. 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 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. FAU - Vegeto, Elisabetta AU - Vegeto E AD - Department of Pharmacological Sciences, Center of Excellence on Neurodegenerative Diseases, University of Milan, via Balzaretti, 9 20133, Italy. FAU - Ghisletti, Serena AU - Ghisletti S FAU - Meda, Clara AU - Meda C FAU - Etteri, Sabrina AU - Etteri S FAU - Belcredito, Silvia AU - Belcredito S FAU - Maggi, Adriana AU - Maggi A LA - eng GR - GP0127Y01/TI_/Telethon/Italy PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - England TA - J Steroid Biochem Mol Biol JT - The Journal of steroid biochemistry and molecular biology JID - 9015483 RN - 0 (DNA, Complementary) RN - 0 (Estrogen Receptor alpha) RN - 0 (Estrogen Receptor beta) RN - 0 (Estrogens) RN - 0 (Lipopolysaccharide Receptors) RN - 0 (Lipopolysaccharides) RN - 0 (Membrane Glycoproteins) RN - 0 (Protein Isoforms) RN - 0 (Receptors, Cell Surface) RN - 0 (Receptors, Estrogen) RN - 0 (Tlr4 protein, rat) RN - 0 (Toll-Like Receptor 4) RN - 0 (Toll-Like Receptors) RN - 4TI98Z838E (Estradiol) RN - EC 3.4.24.35 (Matrix Metalloproteinase 9) SB - IM MH - Animals MH - Animals, Newborn MH - Brain/metabolism MH - Cell Line MH - Cells, Cultured MH - DNA, Complementary/metabolism MH - Enzyme Activation MH - Estradiol/*metabolism MH - Estrogen Receptor alpha MH - Estrogen Receptor beta MH - Estrogens/metabolism MH - Gene Expression Regulation MH - Lipopolysaccharide Receptors/biosynthesis MH - Lipopolysaccharides/*biosynthesis MH - Macrophages/*metabolism MH - Matrix Metalloproteinase 9/biosynthesis MH - Membrane Glycoproteins/biosynthesis MH - Mice MH - Microglia/metabolism MH - Microscopy, Fluorescence MH - Polymerase Chain Reaction MH - Protein Isoforms MH - Rats MH - Rats, Sprague-Dawley MH - Receptors, Cell Surface/biosynthesis MH - Receptors, Estrogen/biosynthesis MH - Reverse Transcriptase Polymerase Chain Reaction MH - *Signal Transduction MH - Time Factors MH - Toll-Like Receptor 4 MH - Toll-Like Receptors EDAT- 2004/07/21 05:00 MHDA- 2004/09/15 05:00 CRDT- 2004/07/21 05:00 PHST- 2003/02/19 00:00 [received] PHST- 2004/02/02 00:00 [accepted] PHST- 2004/07/21 05:00 [pubmed] PHST- 2004/09/15 05:00 [medline] PHST- 2004/07/21 05:00 [entrez] AID - S0960076004002110 [pii] AID - 10.1016/j.jsbmb.2004.02.004 [doi] PST - ppublish SO - J Steroid Biochem Mol Biol. 2004 Jun;91(1-2):59-66. doi: 10.1016/j.jsbmb.2004.02.004.