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Vitamin D and Inflammatory Cytokines in Healthy and Preeclamptic Pregnancies.

Barrera D, Díaz L, Noyola-Martínez N, Halhali A - Nutrients (2015)

Bottom Line: The effects of calcitriol upon inflammatory cytokines has been demonstrated.Finally, the effects of calcitriol upon placental pro-inflammatory cytokines are also explored.In conclusion, maternal and placental calcitriol levels are low in preeclampsia which may explain, at least in part, high pro-inflammatory cytokine levels in this disease.

View Article: PubMed Central - PubMed

Affiliation: Department of Reproductive Biology, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Vasco de Quiroga No. 15, Tlalpan, México D.F. 14000, México. barrera1912@gmail.com.

ABSTRACT
Preeclampsia is a pregnancy disease characterized by hypertension and proteinuria. Among several disorders, the imbalance of inflammatory cytokines and the alteration of vitamin D metabolism have been reported in preeclampsia. The effects of calcitriol upon inflammatory cytokines has been demonstrated. In healthy pregnant women there is a shift toward a Th2 cytokine profile, which is necessary for an adequate pregnancy outcome. As compared with normal pregnancy, high pro-inflammatory and low anti-inflammatory cytokine levels have been observed in preeclamptic women. Preeclampsia has been associated with low calcitriol levels and vitamin D deficiency is correlated with a higher risk of the development of this disease. It has been demonstrated that placenta is a source as well as the target of calcitriol and cytokines and placental dysfunction has been associated with preeclampsia. Therefore, the present manuscript includes a review about serum calcitriol levels in non-pregnant, pregnant, and preeclamptic women as well as a review on the fetoplacental vitamin D metabolism in healthy and preeclamptic pregnancies. In addition, circulating and fetoplacental inflammatory cytokines in healthy and preeclamptic pregnancies are reviewed. Finally, the effects of calcitriol upon placental pro-inflammatory cytokines are also explored. In conclusion, maternal and placental calcitriol levels are low in preeclampsia which may explain, at least in part, high pro-inflammatory cytokine levels in this disease.

No MeSH data available.


Related in: MedlinePlus

Calcitriol effects upon the immune system during pregnancy. Calcitriol regulates several components of the immune system at the systemic and fetoplacental compartments both in immune cells (macrophage, dendritic, uterine natural killer, and lymphocytic) and non-immune cells (trophoblast) leading changes toward a Th2 profile.
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nutrients-07-05293-f001: Calcitriol effects upon the immune system during pregnancy. Calcitriol regulates several components of the immune system at the systemic and fetoplacental compartments both in immune cells (macrophage, dendritic, uterine natural killer, and lymphocytic) and non-immune cells (trophoblast) leading changes toward a Th2 profile.

Mentions: Although low calcitriol concentrations have been found in maternal and umbilical cord compartments from preeclamptic women as compared with normotensive pregnant women [2,3,4,5,6,39], the results of human placental CYP27B1 expression are controversial, depending on the biological material used. Indeed, when CYP27B1 has been studied in syncytiotrophoblast cells in culture, our laboratory has demonstrated low gene expression and activity of this enzyme in preeclampsia [89]. In addition, we have demonstrated that calcitriol was significantly lower in preeclampsia in human placental homogenates obtained from cotyledons [39]. In contrast, in whole human placental tissues, the expression of CYP27B1 mRNA [90] and protein [91] have been found higher in preeclampsia. Decreased placental calcitriol levels seen in preeclampsia may be due to the higher degradation of this secosteroid as a consequence of increased CYP24A1 expression that has been found in preeclampsia [91]. High CYP24A1 expression could be explained by the stimulatory effect of tumor necrosis factor (TNF)-α upon this catabolic enzyme as observed in human cultured trophoblast cells [92,93]. However, it has been observed that the promoter of CYP24A1 is methylated in normal human placenta, a process resulting in the decreased expression of the enzyme, and therefore preventing calcitriol degradation [94]. This observation deserves to be investigated in placentas obtained from preeclamptic women in order to establish if the promoter of CYP24A1 is differentially methylated in this disease in which the milieu is different to that observed in normal pregnancy. In summary, further investigations are needed in order to know if the placental calcitriol clearance is altered in preeclampsia. However, the finding of decreased placental calcitriol synthesis seen in preeclampsia [39,89] may be associated with several alterations of placental functions. Indeed, it has been demonstrated that calcitriol regulated placental human chorionic gonadotropin expression [95], placental steroid hormone secretion [96], placental calbindins expression [97], and placental invasion, as indicated by the increased secretion of matrix prometaloproteinases 2 and 9 by human extravillous trophoblasts [98]. In addition, calcitriol promoted vascular endothelial growth factor and the antioxidant CuZn-superoxide dismutase expression in endothelial cells [99], and reversed the adverse effects of preeclampsia serum or conditioned medium from hypoxic placenta on endothelial colony-forming cells' capillary tube formation and migration [100]. Furthermore, calcitriol has been considered a regulator of placental inflammatory cytokines [93,101,102] (Figure 1) and cytokines have been able to regulate placental CYP27B1 and CYP24A1 expression [92].


Vitamin D and Inflammatory Cytokines in Healthy and Preeclamptic Pregnancies.

Barrera D, Díaz L, Noyola-Martínez N, Halhali A - Nutrients (2015)

Calcitriol effects upon the immune system during pregnancy. Calcitriol regulates several components of the immune system at the systemic and fetoplacental compartments both in immune cells (macrophage, dendritic, uterine natural killer, and lymphocytic) and non-immune cells (trophoblast) leading changes toward a Th2 profile.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4555132&req=5

nutrients-07-05293-f001: Calcitriol effects upon the immune system during pregnancy. Calcitriol regulates several components of the immune system at the systemic and fetoplacental compartments both in immune cells (macrophage, dendritic, uterine natural killer, and lymphocytic) and non-immune cells (trophoblast) leading changes toward a Th2 profile.
Mentions: Although low calcitriol concentrations have been found in maternal and umbilical cord compartments from preeclamptic women as compared with normotensive pregnant women [2,3,4,5,6,39], the results of human placental CYP27B1 expression are controversial, depending on the biological material used. Indeed, when CYP27B1 has been studied in syncytiotrophoblast cells in culture, our laboratory has demonstrated low gene expression and activity of this enzyme in preeclampsia [89]. In addition, we have demonstrated that calcitriol was significantly lower in preeclampsia in human placental homogenates obtained from cotyledons [39]. In contrast, in whole human placental tissues, the expression of CYP27B1 mRNA [90] and protein [91] have been found higher in preeclampsia. Decreased placental calcitriol levels seen in preeclampsia may be due to the higher degradation of this secosteroid as a consequence of increased CYP24A1 expression that has been found in preeclampsia [91]. High CYP24A1 expression could be explained by the stimulatory effect of tumor necrosis factor (TNF)-α upon this catabolic enzyme as observed in human cultured trophoblast cells [92,93]. However, it has been observed that the promoter of CYP24A1 is methylated in normal human placenta, a process resulting in the decreased expression of the enzyme, and therefore preventing calcitriol degradation [94]. This observation deserves to be investigated in placentas obtained from preeclamptic women in order to establish if the promoter of CYP24A1 is differentially methylated in this disease in which the milieu is different to that observed in normal pregnancy. In summary, further investigations are needed in order to know if the placental calcitriol clearance is altered in preeclampsia. However, the finding of decreased placental calcitriol synthesis seen in preeclampsia [39,89] may be associated with several alterations of placental functions. Indeed, it has been demonstrated that calcitriol regulated placental human chorionic gonadotropin expression [95], placental steroid hormone secretion [96], placental calbindins expression [97], and placental invasion, as indicated by the increased secretion of matrix prometaloproteinases 2 and 9 by human extravillous trophoblasts [98]. In addition, calcitriol promoted vascular endothelial growth factor and the antioxidant CuZn-superoxide dismutase expression in endothelial cells [99], and reversed the adverse effects of preeclampsia serum or conditioned medium from hypoxic placenta on endothelial colony-forming cells' capillary tube formation and migration [100]. Furthermore, calcitriol has been considered a regulator of placental inflammatory cytokines [93,101,102] (Figure 1) and cytokines have been able to regulate placental CYP27B1 and CYP24A1 expression [92].

Bottom Line: The effects of calcitriol upon inflammatory cytokines has been demonstrated.Finally, the effects of calcitriol upon placental pro-inflammatory cytokines are also explored.In conclusion, maternal and placental calcitriol levels are low in preeclampsia which may explain, at least in part, high pro-inflammatory cytokine levels in this disease.

View Article: PubMed Central - PubMed

Affiliation: Department of Reproductive Biology, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Vasco de Quiroga No. 15, Tlalpan, México D.F. 14000, México. barrera1912@gmail.com.

ABSTRACT
Preeclampsia is a pregnancy disease characterized by hypertension and proteinuria. Among several disorders, the imbalance of inflammatory cytokines and the alteration of vitamin D metabolism have been reported in preeclampsia. The effects of calcitriol upon inflammatory cytokines has been demonstrated. In healthy pregnant women there is a shift toward a Th2 cytokine profile, which is necessary for an adequate pregnancy outcome. As compared with normal pregnancy, high pro-inflammatory and low anti-inflammatory cytokine levels have been observed in preeclamptic women. Preeclampsia has been associated with low calcitriol levels and vitamin D deficiency is correlated with a higher risk of the development of this disease. It has been demonstrated that placenta is a source as well as the target of calcitriol and cytokines and placental dysfunction has been associated with preeclampsia. Therefore, the present manuscript includes a review about serum calcitriol levels in non-pregnant, pregnant, and preeclamptic women as well as a review on the fetoplacental vitamin D metabolism in healthy and preeclamptic pregnancies. In addition, circulating and fetoplacental inflammatory cytokines in healthy and preeclamptic pregnancies are reviewed. Finally, the effects of calcitriol upon placental pro-inflammatory cytokines are also explored. In conclusion, maternal and placental calcitriol levels are low in preeclampsia which may explain, at least in part, high pro-inflammatory cytokine levels in this disease.

No MeSH data available.


Related in: MedlinePlus