Molecular Medicine

, Volume 14, Issue 7–8, pp 517–527 | Cite as

Estrogen, NFκB, and the Heat Shock Response

  • James P. Stice
  • Anne A. Knowlton
Review Article


Estrogen has pleiotropic actions, among which are its anti-apoptotic, anti-inflammatory, and vasodilatory effects. Recently, an interaction between 17β-estradiol (E2) and the transcription factor nuclear factor κB (NFκB) has been identified. NFκB has a central role in the control of genes involved in inflammation, proliferation, and apoptosis. Prolonged activation of NFκB is associated with numerous inflammatory pathological conditions. An important facet of E2 is its ability to modulate activity of NFκB via both genomic and nongenomic actions. E2 can activate NFκB 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 NFκB and, thus, indirectly inhibit many of its deleterious effects. In addition, HSPs can block NFκB activation and binding directly. Similarly, genomic E2 signaling can inhibit NFκB, but does so through alternative mechanisms. This review focuses on the molecular mechanisms of cross-talk between E2, NFκB, and HSPs, and the biological relevance of this cross-talk.



Supported by NIH HL077281 (AAK), HL079071(AAK), the Department of Veterans Affairs (AAK), and the American Heart Association Western States Affiliate (JPS).


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Copyright information

© Feinstein Institute for Medical Research 2008

Authors and Affiliations

  1. 1.Molecular & Cellular CardiologyUniversity of California, DavisDavisUSA
  2. 2.Cardiovascular Division, Department of Medicine, and the Department of Medical PharmacologyUniversity of California, DavisDavisUSA
  3. 3.The VA Northern California Health Care SystemMatherUSA

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