A pivotal role for the IL-1ß and the inflammasome in preterm labor.

During labor, monocytes infiltrate massively the myometrium and differentiate into macrophages secreting high levels of reactive oxygen species and of pro-inflammatory cytokines (i.e. IL-1ß), leading to myometrial contraction. Although IL-1ß is clearly implicated in labor, its function and that of the inflammasome complex that cleaves the cytokine in its active form, has never been studied on steps preceding contraction. In this work, we used our model of lipopolysaccharide-induced preterm labor to highlight their role. We demonstrated that IL-1ß was secreted by the human myometrium during labor or in presence of infection and was essential for myometrial efficient contractions as its blockage with an IL-1 receptor antagonist (Anakinra) or a neutralizing antibody completely inhibited the induced contractions. We evaluated the implication of the inflammasome on myometrial contractions and differentiation stages of labor onset. We showed that the effects of macrophage-released IL-1ß in myometrial cell transactivation were blocked by inhibition of the inflammasome, suggesting that the inflammasome by producing IL-1ß was essential in macrophage/myocyte crosstalk during labor. These findings provide novel innovative approaches in the management of preterm labor, specifically the use of an inflammasome inhibitor to block the precursor stages of labor before the acquisition of the contractile phenotype.

[Association of polymorphism TaqI of vitamin de receptor with bone mineral density in young Mexican women]. / Asociación del polimorfismo TaqI del gen del receptor de la vitamina D con la densidad mineral ósea en mujeres Mexicanas jóvenes.

INTRODUCTION: Osteoporosis is a multifactorial disease characterized by a low bone mineral density (BMD). Osteoporosis and the occurrence of fractures in postmenopausal women have been associated to the TaqI polymorphism in the vitamin D receptor (VDR) gene. OBJECTIVE: To analyze the association of the different genotypes of TaqI polymorphism of the VDR gene with BMD in young Mexican women. METHODS: Dual X-ray absorptiometry was carried out in 150 women aged 19 to 29 years in order to determine their total bone mineral density (tBMD) and dual BMD of the femur (dfBMD). DNA was extracted from peripheral blood to determine the genotype of the TaqI polymorphism in the VDR gene. The data obtained were analyzed by simple linear regression and ANOVA. RESULTS: Mean tBMD was 1.096 ± 0.064 mean dfBMD was 0.960 ± 0.107 g/cm². The frequency of the TaqI polymorphisms was 57% (TT), 37% (Tt) and 6% (tt), the frequency of the alleles was 75% (T) and 25% (t). Ths statistical analysis showed a lack of association between BMD and the genotypes of TaqI polymorphism in the VDR gene. DISCUSSION AND CONCLUSIONS: These results suggest that may exist factors other than the TaqI polymorphism in the VDR gene contributing to BMD in young women from Northern Mexico.