Different levels of IL-1α, IL-6, TNF-α, NF-κB and PPAR-γ in monocyte cultures exposed by plasma preeclampsia and normotensive pregnancy

Rahardjo, Bambang Tri; Widjajanto, Edy; Sujuti, Hidayat; Keman, Kusnarman

doi:10.1016/j.preghy.2014.03.001

Cited by 30 publications

(25 citation statements)

References 32 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Monocytes and macrophages are the main reservoirs of pro-inflammatory cytokines and are the first cells to be activated in nonspecific immune response. 194 Monocytes produce more TNF-α and IL-6 when treated with plasma from preeclamptic than normal pregnant women. 194 IL-10 may have regulatory effects on monocytes and the inflammatory response during normal pregnancy by controlling TNF-α and IL-1β gene expression, 192 and these IL-10-mediated regulatory effects appear to be lost in preeclampsia.…”

Section: Circulating Bioactive Factors and Mmps In Preeclampsiamentioning

confidence: 99%

Matrix Metalloproteinases in Normal Pregnancy and Preeclampsia

Chen

Khalil

2017

Progress in Molecular Biology and Translational Science

229

168

View full text Add to dashboard Cite

Normal pregnancy is associated with marked hemodynamic and uterine changes that allow adequate uteroplacental blood flow and uterine expansion for the growing fetus. These pregnancy-associated changes involve significant uteroplacental and vascular remodeling. Matrix metalloproteinases (MMPs) are important regulators of vascular and uterine remodeling. Increases in MMP-2 and MMP-9 have been implicated in vasodilation, placentation and uterine expansion during normal pregnancy. The increases in MMPs could be induced by the increased production of estrogen and progesterone during pregnancy. MMP expression/activity may be altered during complications of pregnancy. Decreased vascular MMP-2 and MMP-9 may lead to decreased vasodilation, increased vasoconstriction, hypertensive pregnancy and preeclampsia. Abnormal expression of uteroplacental integrins, cytokines and MMPs may lead to decreased maternal tolerance, apoptosis of invasive trophoblast cells, inadequate remodeling of spiral arteries, and reduced uterine perfusion pressure (RUPP). RUPP may cause imbalance between the anti-angiogenic factors soluble fms-like tyrosine kinase-1 and soluble endoglin and the pro-angiogenic vascular endothelial growth factor and placental growth factor, or stimulate the release of inflammatory cytokines, hypoxia-inducible factor, reactive oxygen species, and angiotensin AT1 receptor agonistic autoantibodies. These circulating factors could target MMPs in the extracellular matrix as well as endothelial and vascular smooth muscle cells, causing generalized vascular dysfunction, increased vasoconstriction and hypertension in pregnancy. MMP activity can also be altered by endogenous tissue inhibitors of metalloproteinases (TIMPs) and changes in the MMP/TIMP ratio. In addition to their vascular effects, decreases in expression/activity of MMP-2 and MMP-9 in the uterus could impede uterine growth and expansion and lead to premature labor. Understanding the role of MMPs in uteroplacental and vascular remodeling and function could help design new approaches for prediction and management of preeclampsia and premature labor.

show abstract

Section: Circulating Bioactive Factors and Mmps In Preeclampsiamentioning

confidence: 99%

Matrix Metalloproteinases in Normal Pregnancy and Preeclampsia

Chen

Khalil

2017

Progress in Molecular Biology and Translational Science

229

168

View full text Add to dashboard Cite

show abstract

Section: Circulating Bioactive Factors In Preeclampsiamentioning

confidence: 99%

“…Monocytes/macrophages are the main reservoir of pro-inflammatory cytokines and are the firstly activated cells in nonspecific immune response (Rahardjo et al, 2014). Monocytes treated with PE plasma produce more TNF-α and IL-6 than cells treated with Norm-Preg plasma (Rahardjo et al, 2014). This is likely due to the regulatory effects of IL-10 on monocytes regulating the inflammatory response that occurs during normal pregnancy by controlling TNF-α and IL-1β gene expression (Matias et al, 2015), and this IL-10-mediated regulatory activity could be lost in PE.…”

Section: Circulating Bioactive Factors In Preeclampsiamentioning

confidence: 99%

Mechanisms of Endothelial Dysfunction in Hypertensive Pregnancy and Preeclampsia

Possomato-Vieira

Khalil

2016

Advances in Pharmacology

184

117

View full text Add to dashboard Cite

Preeclampsia is a pregnancy-related disorder characterized by hypertension, and could lead to maternal and fetal morbidity and mortality. Although the causative factors and pathophysiological mechanisms are unclear, endothelial dysfunction is a major hallmark of preeclampsia. Clinical tests and experimental research have suggested that generalized endotheliosis in the systemic, renal, cerebral and hepatic circulation could decrease endothelium-derived vasodilators such as nitric oxide, prostacyclin and hyperpolarization factor and increase vasoconstrictors such as endothelin-1 and thromboxane A2, leading to increased vasoconstriction, hypertension and other manifestation of preeclampsia. In search for the upstream mechanisms that could cause endothelial dysfunction, certain genetic, demographic and environmental risk factors have been suggested to cause abnormal expression of uteroplacental integrins, cytokines and matrix metalloproteinases, leading to decreased maternal tolerance, apoptosis of invasive trophoblast cells, inadequate spiral arteries remodeling, reduced uterine perfusion pressure (RUPP), and placental ischemia/hypoxia. RUPP may cause imbalance between the anti-angiogenic factors soluble fms-like tyrosine kinase-1 and soluble endoglin and the pro-angiogenic factors vascular endothelial growth factor and placental growth factor, or stimulate the release of other circulating bioactive factors such as inflammatory cytokines, hypoxia-inducible factor-1, reactive oxygen species, and angiotensin AT1 receptor agonistic autoantibodies. These circulating factors could then target endothelial cells and cause generalized endothelial dysfunction. Therapeutic options are currently limited, but understanding the factors involved in endothelial dysfunction could help design new approaches for prediction and management of preeclampsia.

show abstract

“…Preeclampsia is a phenomenon which appears in 5–8% of pregnancies and represents a serious problem concerning both maternal and infant mortality and morbidity [1,2]. Although the precise etiology of preeclampsia is unknown, it has been suggested that while both genetic and environmental factors influence its development, genetic factors have a greater influence, accounting for over half of preeclampsia liability cases [3–5].…”

Section: Introductionmentioning

confidence: 99%

“…Preeclamptic pregnancies have been characterized as a maternal pro-inflammatory state with predominant Th1 and Th17 lymphocytes [12]. Additional sources of pro-inflammatory cytokines (IL-1, TNF-α, IL-6, IL-8) in preeclampsia are monocytes and macrophages [1,11]. Moreover, the blood of preeclamptic women is known to contain elevated levels of such other factors as soluble receptor of IL-6 (sIL-6R), soluble fsm-like tyrosine kinase-1 (sFlt-1), soluble form of Fas ligand (sFasL) and NFĸB [1,13,14].…”

Section: Introductionmentioning

confidence: 99%

Double hit of NEMO gene in preeclampsia

et al. 2017

View full text Add to dashboard Cite

The precise etiology of preeclampsia is unknown. Family studies indicate that both genetic and environmental factors influence its development. One of these factors is NFkB, whose activation depends on NEMO (NFkB essential modulator. This is the first study to investigate the association between the existence of single nucleotide variant of the NEMO gene and the appearance of preeclampsia. A total of 151 women (72 preeclamptic women and 79 controls) and their children were examined. Sanger sequencing was performed to identify variants in the NEMO gene in the preeclamptic mothers. The maternal identified variants were then sought in the studied groups of children, and in the maternal and child controls, using RFLP-PCR. Real-time RT-PCR was performed to assess NEMO gene expression in maternal blood, umbilical cord blood and placentas. The sequencing process indicated the existence of two different variants in the 3'UTR region of the NEMO gene of preeclamptic women (IKBKG:c.*368C>A and IKBKG:c.*402C>T). The simultaneous occurrence of the TT genotype in the mother and the TT genotype in the daughter or a T allele in the son increased the risk of preeclampsia development 2.59 fold. Additionally, we found that the configuration of maternal/fetal genotypes (maternal TT/ daughter TT or maternal TT/son T) of IKBKG:c.*402C/T variant is associated with the level of NEMO gene expression. Our results showed that, the simultaneous occurrence of the maternal TT genotype (IKBKG:c.*402C>T variants) and TT genotype in the daughter or T allele in the son correlates with the level of NEMO gene expression and increases the risk of preeclampsia development. Our observations may offer a new insight into the genetic etiology and pathogenesis of preeclampsia.

show abstract

Different levels of IL-1α, IL-6, TNF-α, NF-κB and PPAR-γ in monocyte cultures exposed by plasma preeclampsia and normotensive pregnancy

Cited by 30 publications

References 32 publications

Matrix Metalloproteinases in Normal Pregnancy and Preeclampsia

Matrix Metalloproteinases in Normal Pregnancy and Preeclampsia

Mechanisms of Endothelial Dysfunction in Hypertensive Pregnancy and Preeclampsia

Double hit of NEMO gene in preeclampsia

Contact Info

Product

Resources

About