17β-Estradiol transcriptionally modulates Nlrp1 and Nlrp3 inflammasomes in gonadectomized rats with inflammation

Context: It has been reported that 17 beta-estradiol (E2) reduces the expression of inflammatory molecules, but there are no data that show the effect of E2 on the transcriptional regulation of innate immunity-related molecules and inflammasomes. Objective: To study the effect of 17 beta-estradiol (E2) on the transcriptional expression of the NLR family, pyrin domain containing 1(Nlrp1) and (Nlrp3) inflammasomes, which are mediators of inflammation. Materials and methods: Inflammation was induced in adult female gonadectomized (Gdx) rats by intramuscular injection of complete Freund's adjuvant (CFA). Measurements were taken at different times after the treatment. Gene expression determinations were done by quantitative real-time polymerase chain reaction (qRT-PCR). Results: CFA-induced inflammation increased the transcription of Nlrp3, IL-1 beta (p < 0.05), vascular cell adhesion molecule 1 (VCAM1), E-selectin and estrogen receptor 1 alpha (ER alpha) (p < 0.001) and decreased the transcription of Nlrp1, Caspase-1, IL-33, NFKB1, ICAM1, ICAM2, GCR alpha, GCR beta, UCP3 and PGC1 alpha (p < 0.001) compared to the control. The administration of E2 to the inflamed tissue significantly increased the expression of Nlrp1, NFKB1, ER alpha, UCP3, Caspase-1, E-selectin (p < 0.001), IL-18 and ER alpha (p < 0.05) and decreased IL-1 beta and VCAM1 (p < 0.005) compared to the control. Discussion and conclusion: CFA differentially modulates the transcription of inflammasome-related genes and the administration of E2 increases the expression of ER alpha and Nlrp1 together with NFKB1, a key molecule in the activation of the inflammasomes. Finally, an analysis using the web interface GeneMANIA revealed an interaction between several genes, indicating a functional correlation in this model.