Progression of vasogenic edema induced by activated microglia under permanent middle cerebral artery occlusion.

Brain edema is a severe complication that accompanies ischemic stroke. Increasing evidence shows that inflammatory cytokines impair tight junctions of the blood-brain barrier, suggesting the involvement of microglia in brain edema. In this study, we examined the role of microglia in the progression of ischemic brain edema using mice with permanent middle cerebral artery occlusion.

Activation of interleukin-6 and -8 expressions by methylmercury in human U937 macrophages involves RelA and p50.

The accumulation of macrophages has been observed around lesions of the brain in patients with Minamata disease. In this condition, mercury has been detected histochemically in macrophages throughout the brain. However, the role of macrophages in the neurotoxicity of methylmercury (MeHg) and the molecular mechanisms of their response to MeHg exposure remain to be elucidated.

Physicochemical properties of iron oxide nanoparticles that contribute to cellular ROS-dependent signaling and acellular production of hydroxyl radical.

While nanoparticles (NPs) are increasingly used in a variety of consumer products and medical applications, some of these materials have potential health concerns. Macrophages are the primary responders to particles that initiate oxidative stress and inflammatory reactions. Here, we utilized six flame-synthesized, engineered iron oxide NPs with various physicochemical properties (e.

Transgenic Overexpression of Aryl Hydrocarbon Receptor Repressor (AhRR) and AhR-Mediated Induction of CYP1A1, Cytokines, and Acute Toxicity.

Background: The aryl hydrocarbon receptor repressor (AhRR) is known to repress aryl hydrocarbon receptor (AhR) signaling, but very little is known regarding the role of the AhRR in vivo.

Objective: This study tested the role of AhRR in vivo in AhRR overexpressing mice on molecular and toxic end points mediated through a prototypical AhR ligand.

Methods: We generated AhRR-transgenic mice (AhRR Tg) based on the genetic background of C57BL/6J wild type (wt) mice.

The role of octopamine receptor agonists in the synergistic toxicity of certain insect growth regulators (IGRs) in controlling Dengue vector Aedes aegypti (Diptera: Culicidae) mosquito.

The synergistic action of octopamine receptor agonists (OR agonists) on many insecticide classes (e.g., organophosphorus, pyrethroids, and neonicotinoids) on Aedes aegypti L.

Suppression of methylmercury-induced IL-6 and MCP-1 expressions by N-acetylcysteine in U-87MG human astrocytoma cells.

Aims: The aim of this study was to clarify the involvement of oxidative stress in methylmercury (MeHg)-induced pro-inflammatory cytokine expressions and the suppressive effects of N-acetylcysteine (NAC) in MeHg-induced cytokine expression.

Materials And Methods: Using U-87-MG human astrocytoma cell line, interleukin (IL)-6 and monocyte chemoattractant protein (MCP)-1 expressions induced by 4 μM MeHg were measured at mRNA and protein levels. Hydrogen peroxide (H2O2) and superoxide anion (O2(-)) were quantified by flow-cytometry analysis.

Unique biochemical and molecular biological mechanism of synergistic actions of formamidine compounds on selected pyrethroid and neonicotinoid insecticides on the fourth instar larvae of Aedes aegypti (Diptera: Culicidae).

We recently reported that formamidine pesticides such as amitraz and chlordimeform effectively synergize toxic actions of certain pyrethroid and neonicotinoid insecticides in some insect species on the 4th instar larvae of Aedes aegypti. Here we studied the biochemical basis of the synergistic actions of the formamidines in amplifying the toxicity of neonicotinoids and pyrethroids such as dinotefuran and thiamethoxam, as well as deltamethrin-fenvalerate type of pyrethroids. We tested the hypothesis that their synergistic actions are mediated by the octopamine receptor, and that the major consequence of octopamine receptor activation is induction of trehalase to increase glucose levels in the hemolymph.

Synergistic action of octopamine receptor agonists on the activity of selected novel insecticides for control of dengue vector Aedes aegypti (Diptera: Culicidae) mosquito.

Studying insecticide resistance in mosquitoes has attracted the attention of many scientists to elucidate the pathways of resistance development and to design novel strategies in order to prevent or minimize the spread and evolution of resistance. Here, we tested the synergistic action of piperonyl butoxide (PBO) and two octopamine receptor (OR) agonists, amitraz (AMZ) and chlordimeform (CDM) on selected novel insecticides to increase their lethal action on the fourth instar larvae of Aedes aegypti L. However, chlorfenapyr was the most toxic insecticide (LC50 = 193, 102, and 48 ng/ml, after 24, 48, and 72 h exposure, respectively) tested.

The aryl hydrocarbon receptor (AhR) mediates resistance to apoptosis induced in breast cancer cells.

The aryl hydrocarbon receptor (AhR) is well known as a ligand binding transcription factor regulating various biological effects. Previously we have shown that long-term exposure to estrogen in breast cancer cells caused not only down regulation of estrogen receptor (ER) but also overexpression of AhR. The AhR interacts with several cell signaling pathways associated with induction of tyrosine kinases, cytokines and growth factors which may support the survival roles of AhR escaping from apoptosis elicited by a variety of apoptosis inducing agents in breast cancer.

Activation of the aryl hydrocarbon receptor by the widely used Src family kinase inhibitor 4-amino-5-(4-chlorophenyl)-7-(dimethylethyl)pyrazolo[3,4-d]pyrimidine (PP2).

Small molecular weight protein kinase inhibitors are frequently used tools to unravel the complex network of cellular signal transduction under certain physiological and pathophysiological conditions. 4-amino-5-(4-chlorophenyl)-7-(dimethylethyl)pyrazolo[3,4-d]pyrimidine (PP2) is a widely used compound to block the activity of Src family kinases, the major group of non-receptor tyrosine kinases, which trigger multiple cellular signaling pathways. Here, we show that PP2 induces cytochrome P450 1A1 mRNA expression and enzyme activity in a dose-dependent manner in human HepG2 hepatoma cells and NCTC 2544 keratinocytes.

Soluble epoxide hydrolase inhibitor attenuates inflammation and airway hyperresponsiveness in mice.

Control of airway inflammation is critical in asthma treatment. Soluble epoxide hydrolase (sEH) has recently been demonstrated as a novel therapeutic target for treating inflammation, including lung inflammation. We hypothesized that pharmacological inhibition of sEH can modulate the inflammatory response in a murine ovalbumin (OVA) model of asthma.

Cross-talk between aryl hydrocarbon receptor and the inflammatory response: a role for nuclear factor-κB.

The aryl hydrocarbon receptor (AhR) is involved in the regulation of immune responses, T-cell differentiation, and immunity. Here, we show that inflammatory stimuli such as LPS induce the expression of AhR in human dendritic cells (DC) associated with an AhR-dependent increase of CYP1A1 (cytochrome P4501A1). In vivo data confirmed the elevated expression of AhR by LPS and the LPS-enhanced 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)-mediated induction of CYP1A1 in thymus of B6 mice.

Aryl hydrocarbon receptor signaling regulates NF-κB RelB activation during dendritic-cell differentiation.

How the aryl hydrocarbon receptor (AhR) regulates dendritic-cell (DC) differentiation is unknown. We show that activation of AhR by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) caused enhanced differentiation from immature DCs (IDCs) to mature DCs (MDCs) in the bone-marrow-derived DCs (BMDC) from B6 wild-type mice but not in the BMDCs from AhR-null mice as indicated by the expression of CD11c and class II major histocompatibility complex (MHC). Enhanced maturation of BMDCs was associated with elevated levels of CD86 and an increased AhR-dependent nuclear accumulation of nuclear factor-kappa-light-chain enhancer of activated B cell (NF-κB) member RelB in BMDCs.

Combustion-derived flame generated ultrafine soot generates reactive oxygen species and activates Nrf2 antioxidants differently in neonatal and adult rat lungs.

Background: Urban particulate matter (PM) has been epidemiologically correlated with multiple cardiopulmonary morbidities and mortalities, in sensitive populations. Children exposed to PM are more likely to develop respiratory infections and asthma. Although PM originates from natural and anthropogenic sources, vehicle exhaust rich in polycyclic aromatic hydrocarbons (PAH) can be a dominant contributor to the PM2.

Combustion derived ultrafine particles induce cytochrome P-450 expression in specific lung compartments in the developing neonatal and adult rat.

Vehicle exhaust is rich in polycyclic aromatic hydrocarbons (PAH) and can be a dominant contributor to ultrafine urban particulate matter (PM). Exposure to ultrafine PM is correlated with respiratory infections and asthmatic symptoms in young children. The lung undergoes substantial growth, alveolarization, and cellular maturation within the first years of life, which may be impacted by environmental pollutants such as PM.

Activation of inflammatory responses in human U937 macrophages by particulate matter collected from dairy farms: an in vitro expression analysis of pro-inflammatory markers.

Background: The purpose of the present study was to investigate activation of inflammatory markers in human macrophages derived from the U937 cell line after exposure to particulate matter (PM) collected on dairy farms in California and to identify the most potent components of the PM.

Methods: PM from different dairies were collected and tested to induce an inflammatory response determined by the expression of various pro-inflammatory genes, such as Interleukin (IL)-8, in U937 derived macrophages. Gel shift and luciferase reporter assays were performed to examine the activation of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) and Toll-like-receptor 4 (TLR4).

Association of serum levels of polychlorinated biphenyls with IL-8 mRNA expression in blood samples from asthmatic and non-asthmatic Japanese children.

Background: One of the suggested health outcomes of PCB exposure is childhood asthma.

Objectives: This study was conducted to find health relevant biomarkers providing the molecular epidemiological evidence for the positive relationship between exposure to PCBs and childhood asthma.

Methods: Blood samples from fifteen asthmatic children as well as an equal number of non-asthmatic children (average 2 year old) were collected, and were analyzed for PCBs and their select marker expression by using qRT-PCR.

AhR deficiency impairs expression of LPS-induced inflammatory genes in mice.

Recent reports suggest the participation of the aryl hydrocarbon receptor (AhR) in the induction mechanism of the NF-κB signaling pathway. In the current study we challenged C57BL/6 wild-type (WT) and AhR deficient (AhR(-/-)) mice with bacterial lipopolysaccharide (LPS) to investigate the role of the AhR in expression profiles of LPS and NF-κB target genes. Further, we analyzed the effect of LPS on the DNA binding activity of NF-κB, C/EBP and AP-1 transcription factors in liver and lung from WT and AhR(-/-) mice.

Interaction of aryl hydrocarbon receptor and NF-κB subunit RelB in breast cancer is associated with interleukin-8 overexpression.

The aryl hydrocarbon receptor (AhR) has been best known for its role in mediating the toxicity of dioxin. Here we show that AhR overexpression is found among estrogen receptor (ER)α-negative human breast tumors and that its overexpression is positively correlated to that of the NF-κB subunit RelB and Interleukin (IL)-8. Increased DNA binding activity of the AhR and RelB is coupled to IL-8 overexpression in primary breast cancer tissue, which was also supported by in situ hybridization.

Suppression of WIF-1 through promoter hypermethylation causes accelerated proliferation of the aryl hydrocarbon receptor (AHR) overexpressing MCF10AT1 breast cancer cells.

The cause for increased cell proliferation in AHR overexpressing breast cancer cells still remains unknown. Here we studied the molecular basis of aggressive cell proliferation of an AHR overexpressing and ERα functionally down-regulated MCF10AT1 cell line, designated as P20E, in comparison to a matched sub-line, P20C with normal AHR expression and ERα function. We found that a 4-day treatment of P20E cells with 5-aza-2'-deoxycytidine (AZ) caused a significant suppression of cell proliferation.

Activation of aryl hydrocarbon receptor induces vascular inflammation and promotes atherosclerosis in apolipoprotein E-/- mice.

Objective: Exposure to dioxins has been shown to contribute to the development of inflammatory diseases, such as atherosclerosis. Macrophage-mediated inflammation is a critical event in the initiation of atherosclerosis. Previously, we showed that treatment of macrophages with 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) leads to aryl hydrocarbon receptor (AhR)-dependent activation of inflammatory mediators and the formation of cholesterol-laden foam cells.

FRET analysis of protein tyrosine kinase c-Src activation mediated via aryl hydrocarbon receptor.

Background: Activation of the protein tyrosine kinase c-Src (c-Src kinase) induced by the exposure to the environmental pollutant 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) has been shown in various cell types. Most previous works used Western blot analysis to detect the phosphorylation on the Tyr416 residue, which activates c-Src kinase.

Methods: Here we compared the results of c-Src tyrosine phosphorylation via aryl hydrocarbon receptor (AhR)-dependent mechanisms from Western blot analysis with fluorescent resonance energy transfer (FRET) assay detecting c-Src activation after treatment with TCDD to activate AhR in two different human cell types.

Effects of selected food phytochemicals in reducing the toxic actions of TCDD and p,p'-DDT in U937 macrophages.

To assess the effectiveness of selected food phytochemicals in reducing the toxic effects of the environmental toxicants, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and p,p'-DDT (DDT), we tested the potencies of auraptene, nobiletin, zerumbone, and (±)-13-hydroxy-10-oxo-trans-11-octadecenoic acid (13-HOA) in reversing the inflammatory action of these toxicants in U937 human macrophages. Using quantitative RT-PCR as the initial screening assay, we identified antagonistic actions of zerumbone and auraptene against the action of TCDD and DDT in up-regulating the mRNA expressions of COX-2 and VEGF. The functional significance of the inhibitory action of zerumbone on COX-2 expression was confirmed by demonstrating its suppression of TCDD-induced activation of COX-2 gene expression in mouse MMDD1 cells.

Non-genomic action of TCDD to induce inflammatory responses in HepG2 human hepatoma cells and in liver of C57BL/6J mice.

To assess the significance of the non-genomic signaling of TCDD (=dioxin) on liver of C57BL/6 mice and HepG2 human hepatoma cells, we first determined the group of markers that are susceptible to inhibition by parthenolide, a compound known to specifically suppress NF-κB-mediated inflammation. Of those, the most consistent marker turned out to be SOCS3 (a suppressor of cytokine signaling) known to respond to inflammation. An early diagnostic test on the action of TCDD on HepG2 cells in vitro within 3-6 h indicated that Cox-2 and SOCS3 are mainly induced via a non-genomic route, whereas PAI-2 appears to be induced through the classical action route.

TCDD-induced cyclooxygenase-2 expression is mediated by the nongenomic pathway in mouse MMDD1 macula densa cells and kidneys.

Cyclooxygenase-2 (Cox-2) plays a critical role in TCDD-induced hydronephrosis in mouse neonates. In this study we found that induction of Cox-2 by TCDD in MMDD1, a mouse macula densa cell line, is accompanied with a rapid increase in the enzymatic activity of cytosolic phospholipase A2 (cPLA2) as well as activation of protein kinases. Calcium serves as a trigger for such an action of TCDD in this cell line.