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Modulation of NALP3 Inflammasome Genes by EstrogenChesnokov, Anton P, Mr. 27 August 2011 (has links)
Immunity is known to be sexually dimorphic. This dimorphism may be attributed to the action of different hormones. Aluminum is a component of several vaccines and acts as an adjuvant of immunogenicity. The activation of the Nalp3 inflammasome plays a role in aluminum’s adjuvancy. Estrogen affects immune cells by regulating the expression of genes involved in immune-related mechanisms; such as the modulation of cytokine secretion. We hypothesized that estrogen modulates the aluminum-induced secretion of IL-1β and IL-18. Using an ex vivo mouse macrophage model this study examined: (i) the effects of estrogen on Nalp3 inflammasome genes expression and (ii) the estrogen receptor involved in the modulation of these genes. Our results indicate that estrogen up-regulates Nalp3 gene expression via ERα/β heterodimerization, and caspase-1 activity may be indirectly modulated due to the up-regulation of SPI-6 via ERβ.
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