Estrogen, NFκB, and the heat shock response

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