title: Estrogen, NFkappaB, and the heat shock response.
abstract: Estrogen has pleiotropic actions, among which are its anti-apoptotic, anti-inflammatory, and vasodilatory effects. Recently, an interaction between 17beta-estradiol (E2) and the transcription factor nuclear factor kappaB (NFkappaB) has been identified. NFkappaB has a central role in the control of genes involved in inflammation, proliferation, and apoptosis. Prolonged activation of NFkappaB is associated with numerous inflammatory pathological conditions. An important facet of E2 is its ability to modulate activity of NFkappaB via both genomic and nongenomic actions. E2 can activate NFkappaB rapidly via nongenomic pathways, increase cellular resistance to injury, and induce expression of the protective class of proteins, heat shock proteins (HSPs). HSPs can bind to many of the pro-apoptotic and pro-inflammatory targets of NFkappaB and, thus, indirectly inhibit many of its deleterious effects. In addition, HSPs can block NFkappaB activation and binding directly. Similarly, genomic E2 signaling can inhibit NFkappaB, but does so through alternative mechanisms. This review focuses on the molecular mechanisms of cross-talk between E2, NFkappaB, and HSPs, and the biological relevance of this cross-talk.
authors.affiliation: Molecular & Cellular Cardiology, University of California, Davis, California, USA.
authors.forename: James P
authors.initials: JP
authors.lastname: Stice
authors.forename: Anne A
authors.initials: AA
authors.lastname: Knowlton
mesh_terms: D000818:Animals; D002318:Cardiovascular Diseases / Q000209:etiology; D019610:Cytoprotection / Q000187:drug effects / Q000502:physiology; D004967:Estrogens / Q000494:pharmacology / Q000502:physiology*; D006360:Heat-Shock Proteins / Q000502:physiology; D018869:Heat-Shock Response / Q000502:physiology*; D006801:Humans; D008954:Models, Biological; D016328:NF-kappa B / Q000502:physiology*; D012727:Sex Characteristics; D013312:Stress, Physiological / Q000503:physiopathology
chemical_list: D004967:Estrogens; D006360:Heat-Shock Proteins; D016328:NF-kappa B