TY - JOUR
T1 - 17β-Estradiol transcriptionally modulates Nlrp1 and Nlrp3 inflammasomes in gonadectomized rats with inflammation
AU - Gómez López, Modesto
AU - Domínguez López, Aarón
AU - Abarca Rojano, Edgar
AU - Rojas Hernández, Saúl
AU - Martínez Godínez, María De Los A.
AU - Miliar García, Angel
AU - Campos Rodríguez, Rafael
N1 - Publisher Copyright:
© 2015 Informa Healthcare USA, Inc. All rights reserved.
PY - 2015/7/4
Y1 - 2015/7/4
N2 - Context: It has been reported that 17β-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 17β-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-1β (p < 0.05), vascular cell adhesion molecule 1 (VCAM1), E-selectin and estrogen receptor 1 alpha (ERα) (p < 0.001) and decreased the transcription of Nlrp1, Caspase-1, IL-33, NFKB1, ICAM1, ICAM2, GCRα, GCRβ, UCP3 and PGC1α (p < 0.001) compared to the control. The administration of E2 to the inflamed tissue significantly increased the expression of Nlrp1, NFKB1, ERα, UCP3, Caspase-1, E-selectin (p < 0.001), IL-18 and ERα (p < 0.05) and decreased IL-1β 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 ERα 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.
AB - Context: It has been reported that 17β-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 17β-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-1β (p < 0.05), vascular cell adhesion molecule 1 (VCAM1), E-selectin and estrogen receptor 1 alpha (ERα) (p < 0.001) and decreased the transcription of Nlrp1, Caspase-1, IL-33, NFKB1, ICAM1, ICAM2, GCRα, GCRβ, UCP3 and PGC1α (p < 0.001) compared to the control. The administration of E2 to the inflamed tissue significantly increased the expression of Nlrp1, NFKB1, ERα, UCP3, Caspase-1, E-selectin (p < 0.001), IL-18 and ERα (p < 0.05) and decreased IL-1β 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 ERα 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.
KW - Adjuvant
KW - estrogens
KW - gene expression
KW - inflammasome
KW - inflammation
UR - http://www.scopus.com/inward/record.url?scp=84938885505&partnerID=8YFLogxK
U2 - 10.3109/08923973.2015.1059439
DO - 10.3109/08923973.2015.1059439
M3 - Artículo
C2 - 26153911
SN - 0892-3973
VL - 37
SP - 343
EP - 350
JO - Immunopharmacology and Immunotoxicology
JF - Immunopharmacology and Immunotoxicology
IS - 4
ER -