Progesterone and vitamin D downregulate the activation of the NLRP1/NLRP3 inflammasomes and TLR4-MyD88-NF-κB pathway in monocytes from pregnant women with preeclampsia.

This study evaluated the in vitro modulatory effect of progesterone (PG) and vitamin D (VD) on NLRP1/NLRP3 inflammasomes and TLR4/NF-κB pathway in monocytes from pregnant women with preeclampsia (PE). Monocytes from 20 preeclamptic and 20 normotensive (NT) pregnant women, and THP-1 cells were cultured with/without hyaluronan (HA), PG, or VD to determine gene and protein expression of TLR4 receptor, phosphorylated NF-κB, IκBα, TLR4, MYD88, NF-κB, NLRP1, NLRP3, caspase-1, IL-1β, IL-18, TNF-α, and IL-10. Higher endogenous activation of inflammatory genes and higher protein expression of TLR4 and NF-κB was detected in monocytes of PE group and decreased after PG or VD treatment.

Downregulation of CD163 in monocytes and its soluble form in the plasma is associated with a pro-inflammatory profile in pregnant women with preeclampsia.

Preeclampsia (PE) is a pregnancy-specific syndrome characterized by a systemic inflammatory response that polarizes peripheral blood monocytes to the M1 phenotype. The classically activated M1 monocytes comprise immune effector cells with an acute inflammatory phenotype. CD163 is a scavenger receptor expressed by monocytes/macrophages that may be shed from their cell membrane after proteolytic cleavage, producing the soluble CD163 molecule (sCD163).

Increased expression of NLRP3 inflammasome in placentas from pregnant women with severe preeclampsia.

Preeclampsia is a pregnancy disorder characterized by imbalance between pro- and anti-inflammatory cytokines associated with high plasma levels of uric acid and Interleukin-1 beta (IL-1β). The inflammasome is a protein complex that mediates innate immune responses via caspase-1 activation promoting secretion of IL-1β and IL-18 in their active forms, and also release of the high-mobility group box 1 protein (HMGB1). As the placenta seems to play an important role in the pathogenesis of PE, the present study investigated the expression of genes and proteins related to the inflammasome in placentas from pregnant women with severe preeclampsia.

Elevated circulatingadenosine deaminase activity in women with preeclampsia: association with pro-inflammatory cytokine production and uric acid levels.

Objective: Preeclampsia is a specific disorder of human pregnancy that is associated with hyperuricemia and higher levels of pro-inflammatory cytokines. Adenosine deaminase (ADA) is an enzyme present in all human tissues, and is considered an indicator of cellular inflammation. In the present study we assess whether adenosine deaminase (ADA) activity is altered in women with preeclampsia (PE) and contributes to elevated levels of uric acid and pro-inflammatory cytokine production.

Association between Placental Lesions, Cytokines and Angiogenic Factors in Pregnant Women with Preeclampsia.

Preeclampsia (PE) is considered the leading cause of maternal and perinatal morbidity and mortality. The placenta seems to play an essential role in this disease, probably due to factors involved in its formation and development. The present study aimed to investigate the association between placental lesions, cytokines and angiogenic factors in pregnant women with preeclampsia (PE).

Endogenous and Uric Acid-Induced Activation of NLRP3 Inflammasome in Pregnant Women with Preeclampsia.

Preeclampsia (PE) is a specific syndrome of pregnancy, characterized by hypertension and proteinuria. This pathology is associated with hyperuricemia and elevated serum levels of inflammatory cytokines. Uric acid crystals may activate an intracellular complex called inflammasome, which is important for processing and release of inflammatory cytokines.

Monocytes from pregnant women with pre-eclampsia are polarized to a M1 phenotype.

Problem: This study evaluated whether the monocyte inflammatory state in pre-eclampsia (PE) might be associated with polarization to either M1 classically or M2 alternatively activated monocyte subsets.

Method Of Study: Eighty-five women with (PE) and 52 normotensive (NT) pregnant women matched for gestational age were included. Expression of surface receptors characteristic of M1, such as Toll-like receptor (TLR)2, TLR4, and CD64, or M2, such as CD163 and CD206 monocyte subsets were evaluated in peripheral blood monocytes by flow cytometry.

The 60- and 70-kDa heat-shock proteins and their correlation with cardiovascular risk factors in postmenopausal women with metabolic syndrome.

We investigated the association between circulating levels of 60 and 70 kDa heat-shock proteins (HSP60 and 70) and cardiovascular risk factors in postmenopausal women with or without metabolic syndrome (MetS). This cross-sectional study included 311 Brazilian women (age ≥45 years with amenorrhea ≥12 months). Women showing three or more of the following diagnostic criteria were diagnosed with MetS: waist circumference (WC) ≥88 cm, blood pressure ≥130/85 mmHg, triglycerides ≥150 mg/dl, high-density lipoprotein (HDL) <50 mg/dl, and glucose ≥100 mg/dl.

High levels of heat shock protein 70 are associated with pro-inflammatory cytokines and may differentiate early- from late-onset preeclampsia.

Preeclampsia (PE), a specific syndrome of pregnancy, can be classified into early and late onset, depending on whether clinical manifestations occur before or after 34 weeks' gestation. We determined whether plasma concentrations of Hsp60 and Hsp70 were related to circulating cytokine levels, as well as kidney and liver functions, in early- and late-onset PE. Two hundred and thirty-seven preeclamptic women (95 with early- and 142 with late-onset PE) were evaluated.

Elevated hyaluronan and extracellular matrix metalloproteinase inducer levels in women with preeclampsia.

Purpose: Preeclampsia (PE) is a specific syndrome of pregnancy clinically identified by hypertension and proteinuria from the 20th week of gestation associated with a systemic inflammatory response and oxidative stress. While pro-inflammatory cytokines have been extensively studied in PE, other factors in the circulation that also influence the magnitude of inflammation have received much less attention. The present study compared serum concentrations of five immune-regulatory compounds in normotensive pregnant women and in women with gestational hypertension (GH) or PE.

sFlt-1/PlGF ratio as a prognostic marker of adverse outcomes in women with early-onset preeclampsia.

Soluble fms-like tyrosine kinase 1 (sFlt-1) is an anti-angiogenic factor released in higher amounts by preeclamptic placentas and it has been implicated in the endothelial dysfunction observed in the disease. In this study we evaluated if circulating sFlt-1/PlGF ratio is useful to predict adverse outcomes in women with early-onset preeclampsia. This is a cohort study of 88 preeclamptic women with singleton pregnancies at ⩽35weeks of gestation.

Silibinin modulates the NF-κb pathway and pro-inflammatory cytokine production by mononuclear cells from preeclamptic women.

Preeclampsia (PE) is a complication of human pregnancy associated with an intense inflammatory response involving leukocyte activation, as well as elevated production of pro-inflammatory cytokines. The nuclear transcription factor-kappa B (NF-κB) is present in cells of the immune system and is responsible for transcription of genes coding for pro-inflammatory proteins. Silibinin is the main component of silymarin, a polyphenolic extract obtained from fruits and seeds of Silybum marianum with potent hepatoprotective and anti-inflammatory activities.

Hepatoprotective and anti-inflammatory effects of silibinin on experimental preeclampsia induced by L-NAME in rats.

Aims: Inhibition of nitric oxide synthase with N-omega-nitro-l-arginine methyl ester (l-NAME) has been employed as an experimental model of human preeclampsia. This study determined the protective effect of silibinin, a flavonoid with anti-inflammatory and hepatoprotective properties on the deleterious effects observed in experimentally induced preeclampsia in rats.

Main Methods: Pregnant Wistar rats were treated during gestation (days 10-20) with l-NAME (70-80mg/kg/day) in drinking water or with l-NAME plus silibinin (100mg/kg/day, orally) starting at day 0, day 7 or day 14 of pregnancy.

Granulocyte macrophage colony-stimulating factor enhances the modulatory effect of cytokines on monocyte-derived multinucleated giant cell formation and fungicidal activity against Paracoccidioides brasiliensis.

Multinucleated giant cells (MGC) are cells present in characteristic granulomatous inflammation induced by intracellular infectious agents or foreign materials. The present study evaluated the modulatory effect of granulocyte macrophage colony-stimulating factor (GM-CSF) in association with other cytokines such as interferon-gamma (IFN-γ), tumour necrosis factor-alpha, interleukin (IL)-10 or transforming growth factor beta (TGF-β1) on the formation of MGC from human peripheral blood monocytes stimulated with Paracoccidioides brasiliensis antigen (PbAg). The generation of MGC was determined by fusion index (FI) and the fungicidal activity of these cells was evaluated after 4 h of MGC co-cultured with viable yeast cells of P.

Increased reactive oxygen species and tumor necrosis factor-alpha production by monocytes are associated with elevated levels of uric acid in pre-eclamptic women.

Problem: To evaluate associations between hyperuricemia and increases in production of reactive oxygen species (ROS) and tumor necrosis factor alpha (TNF-α) in pre-eclamptic pregnancies.

Method Of Study: This study investigated serum uric acid levels, monocyte production of TNF-α, superoxide anion (O(2)(-)) and hydrogen peroxide (H(2)O(2)), as well as superoxide dismutase (SOD) and catalase (CAT) activities in erythrocytes from 30 women with pre-eclampsia (PE) compared with 30 normotensive (NT) pregnant women in the last trimester of pregnancy.

Results: Serum uric acid levels (6.

sFlt-1 and IP-10 in women with early-onset preeclampsia.

Intense inflammatory response and an anti-angiogenic state have been implicated in the pathogenesis of preeclampsia. Here, we investigated this hypothesis evaluating the serum concentrations of CXCL10/IP-10, sFlt-1, and PlGF in women with early-onset preeclampsia. CXCL10/IP-10 was measured by Cytometric Bead Array.

Interactions between TLR2, TLR4, and mannose receptors with gp43 from Paracoccidioides brasiliensis induce cytokine production by human monocytes.

The glycoprotein gp43 is an immunodominant antigen secreted by Paracoccidioides brasiliensis, the agent of paracoccidioidomycosis. The present study evaluated whether gp43 can interact with toll-like (TLR2, TLR4) and mannose (MR) receptors on the surface of human monocytes, and how that affects their expression and cytokine production. Monocytes were incubated with or without monoclonal antibodies anti-TLR2, anti-TLR4, or anti-MR, individually or in combination, prior to the addition of gp43.

Interleukin-15 augments oxidative metabolism and fungicidal activity of human monocytes against Paracoccidioides brasiliensis.

Interleukin (IL)-15 is a pleiotropic cytokine that regulates the proliferation and survival of many cell types. IL-15 is produced by monocytes and macrophages against infectious agents and plays a pivotal role in innate and adaptive immune responses. This study analyzed the effect of IL-15 on fungicidal activity, oxidative metabolism and cytokine production by human monocytes challenged in vitro with Paracoccidioides brasiliensis (Pb18), the agent of paracoccidioidomycosis.

Genetic and modifying factors that determine the risk of brain tumors.

Some modifying factors may determine the risk of brain tumors. Until now, it could not be attempted to identify people at risk and also to improve significantly disease progression. Current therapy consists of surgical resection, followed by radiation therapy and chemotherapy.

Downregulation of nuclear factor-kappa B (NF-kappaB) pathway by silibinin in human monocytes challenged with Paracoccidioides brasiliensis.

Aims: Silibinin is the major active component of silymarin, a polyphenolic plant flavonoid that has anti-inflammatory effects. The modulatory effect of silibinin on monocyte function against Paracoccidioides brasiliensis (Pb18) has not yet been demonstrated. The present study investigated whether the effect of silibinin on nuclear factor-kappa B (NF-kappaB) pathways may affect the production of tumor necrosis factor-alpha (TNF-alpha), interleukin-10 (IL-10), transforming growth factor beta (TGF-beta1), prostaglandin E(2) (PGE(2)), nitric oxide (NO) and fungicidal activity of human monocytes challenged in vitro with Pb18.

Platelet aggregation and TGF-beta(1) plasma levels in pregnant women with preeclampsia.

Objectives: Platelets and transforming growth factor-beta(1) (TGF-beta(1)) are thought to be involved in the pathogenesis of preeclampsia. Our objectives were to determine plasma concentration of TGF-beta(1) in normotensive and preeclamptic women in the third trimester of pregnancy and to evaluate the correlation of TGF-beta(1) plasma levels with platelet count and agonist-induced aggregation capacity.

Methods: Thirty-three women with preeclampsia were compared with 36 healthy women with uncomplicated pregnancies.

Interleukin-6 treatment enhances human monocyte permissiveness for Paracoccidioides brasiliensis growth by modulating cytokine production.

The effect of interleukin (IL)-6 on cytokine production was evaluated in human monocyte cultures infected with the virulent strain of Paracoccidioides brasiliensis (Pb18). Peripheral blood monocytes from healthy individuals were preincubated for 24 h with or without human recombinant IL-6, and then challenged with Pb18 for 4 h and 18 h. P.

Experimental infections with Paracoccidioides brasiliensis obtained from armadillos: comparison to clinical isolates.

Paracoccidioides brasiliensis causes paracoccidioidomycosis (PCM) that is one of the most prevalent systemic human mycoses in Latin America. Armadillos show a high incidence of PCM infection and could, therefore, be a natural reservoir for this fungus. In this study were compared the virulence profiles of isolates obtained from nine-banded armadillos (Dasypus novemcinctus) (PbT1 and PbT4) and isolates from PCM patients (Pb265 and Bt83).

Killing of Paracoccidioides brasiliensis yeast cells by IFN-gamma and TNF-alpha activated murine peritoneal macrophages: evidence of H(2)O (2) and NO effector mechanisms.

Paracoccidioidomycosis is a deep mycosis, endemic in Latin America, caused by Paracoccidioides brasiliensis. Macrophage activation by cytokines is the major effector mechanism against this fungus. This work aimed at a better understanding of the interaction between yeast cells-murine peritoneal macrophages and the cytokine signals required for the effective killing of high virulence yeast-form of P.

Fungicidal activity of human monocyte-derived multinucleated giant cells induced in vitro by Paracoccidioides brasiliensis antigen.

Multinucleated giant cells (MGC) are characteristic cells in granulomatous disorders such as paracoccidioidomycosis (PCM) and also are formed in vitro from peripheral blood mononuclear cells by several stimuli. In this study, the authors investigated in vitro formation of MGC derived from monocytes of healthy individuals, stimulated with Paracoccidioides brasiliensis antigen (PbAg), compared with other stimuli such as IFN-gamma and supernatant of Con-A-stimulated peripheral blood mononuclear cells (CM-ConA). Besides, the fungicidal activity of monocytes and monocyte-derived MGC challenged with P.