Estrogen inhibits NF kappa B-dependent inflammation in brain endothelium without interfering with I kappa B degradation.
The protective effects of 17beta-estradiol in cerebral ischemia may be partially due to the blockade of leukocyte adhesion in cerebral endothelial cells, although the molecular mechanisms are not well understood. We report that 17beta-estradiol (E(2)), but not the alpha-enantiomer, inhibited the basal and interleukin-1beta (IL-1beta)-mediated expression of the intercellular adhesion molecule type 1 (ICAM1) and NFkappaB activation, in cultured brain endothelial cells. However, the degradation of IkappaB-alpha, which is an essential requirement for the translocation of NFkappaB to the nucleus, and a common biological target to suppress NFkappaB activation, was not halted by E(2). These findings indicate that decreased expression of adhesion molecules may account for the capacity E(2) to reduce adhesion of leukocytes in cerebral endothelium in vivo, and suggest the existence of brain-specific, estrogen-sensitive pathways, other than IkappaB-alpha_-regulation, to modulate NFkappaB. The stereoselectivity of the E(2) effect is consistent with an estrogen receptor-mediated mechanism.
Galea
Elena
E
Neuroanesthesia Research Laboratory, Department of Anesthesiology (MC 519), University of Illinois at Chicago, 1819 W. Polk St, Chicago, IL 60612, USA.
Santizo
Roberto
R
Feinstein
Douglas L
DL
Adamsom
Peter
P
Greenwood
John
J
Koenig
Heidi M
HM
Pelligrino
Dale A
DA
D000818:Animals; D001921:Brain / Q000098:blood supply* / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D002461:Cell Line, Transformed; D004268:DNA-Binding Proteins / Q000378:metabolism*; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology*; D004958:Estradiol / Q000494:pharmacology* / Q000502:physiology; D020672:I-kappa B Proteins; D007249:Inflammation / Q000378:metabolism / Q000517:prevention & control; D018799:Intercellular Adhesion Molecule-1 / Q000096:biosynthesis; D000072000:NF-KappaB Inhibitor alpha; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000378:metabolism*; D051381:Rats
D004268:DNA-Binding Proteins; D020672:I-kappa B Proteins; D016328:NF-kappa B; C000606206:Nfkbia protein, rat; D018799:Intercellular Adhesion Molecule-1; D000072000:NF-KappaB Inhibitor alpha; D004958:Estradiol