benzodiazepins monocytes

Downregulation of cell surface β-adrenergic receptors (β-AR) is an important adaptive response that prevents deleterious effects of receptor overstimulation. Various factors including reactive oxygen species cause β-AR downregulation. In this study, we evaluated the effects of ligands of the peripheral benzodiazepine receptor (PBR), a key protein in regulating oxidative stress, on surface density of endogenous β1 -and β2 -ARs in highly differentiated cells such as human monocytes, which express both β-AR subtypes...

BACKGROUND: Benzodiazepines are widely used for anesthesia and sedation and have immunomodulatory properties that may negatively influence clinical outcomes; however, the cellular targets and intermediary signaling pathways involved are unclear. We examined the immunomodulatory effects of the benzodiazepine midazolam on human macrophages and associated molecular mechanisms. METHODS: We analyzed effects of midazolam pretreatment on lipopolysaccharide (LPS)-induced upregulation of the costimulatory molecule CD80 and secretion of the pro-inflammatory factors interleukin-6 (IL-6), tumor necrosis factor-α, interleukin-10, and nitric oxide (NO) in the human monocyte-macrophage cell line THP-1 and in peripheral monocyte-derived macrophages (PMDMs)...

OBJECTIVE: Psychosocial stress is associated with altered immunity, anxiety, and depression. Repeated social defeat (RSD), a model of social stress, triggers egress of inflammatory myeloid progenitor cells (MPCs; CD11b(+)/Ly6C(hi)) that traffic to the brain, promoting anxiety-like behavior. In parallel, RSD enhances neuroinflammatory signaling and long-lasting social avoidant behavior. Lorazepam and clonazepam are routinely prescribed anxiolytics that act by enhancing GABAergic activity in the brain...

Benzodiazepines increase vulnerability to infection through α1 subunit dependent Υ-amino-butyric-type-A (GABAA) signalling. Immune cell expression of GABAA receptors and the effect of diazepam on influenza infection was investigated. In patients with pneumonia, α1 GABAA subunits were expressed on alveolar macrophages and blood monocytes. In mice, influenza induced dynamic changes in immune cell GABAA subunit expression: α1 subunits decreased on alveolar macrophage, but increased on monocytes, CD4+ and CD8+ T cells...

Monocytes have been isolated from patient's blood and directly radiolabelled in vitro using a variety of radiopharmaceuticals such as 99mTc-HMPAO, 111In-oxine, 99mTc-colloids and 18F-FDG. Overall, the best labeling results were obtained using 99mTc-HMPAO. The wide availability of 99mTc and of the ligand HMPAO in kit-formulation makes it the most versatile procedure for imaging localized inflammation using in-vitro labeling. Injection of 99mTc-HMPAO labeled monocytes in adult patients has proven safe with an effective dose of 0...

Amyotrophic Lateral Sclerosis (ALS) is a neurodegenerative disorder that affects upper and lower motor neurons. Previous evidence has indicated that excitotoxic cell death in ALS may remarkably depend on Cl(-) ion influx through the GABA(A) receptors. In this study we have analysed the effect of Monocyte Chemoattractant Protein-1 (MCP-1), a chemokine expressed to a higher level in ALS patients, on GABAA receptors in cultured cortical neurons from a genetic model of ALS (G93A) and compared with wild type SOD1 (SOD1) and their corresponding non transgenic littermates (Control)...

OBJECTIVES: Benzodiazepines are used for treating anxiety, epilepsy, muscle spasm, alcohol withdrawal, palliation, insomnia, and sedation as they allosterically modulate γ-amino-butyric acid type A (GABAA) receptors. Despite widespread use, the importance and mechanism of their immune side-effects are poorly understood. Herein we sought to elucidate the impact and mechanism of benzodiazepine-induced susceptibility to infection at anxiolytic doses in mice. DESIGN: Animal randomized controlled trial...

Peripheral benzodiazepine receptor (PBR) is a multifunctional protein mainly found on the outer mitochondrial membrane. PBR expression is increased by tumor necrosis factor-α (TNF-α) in endothelial cells. Adenoviral overexpression of PBR inhibits monocyte adhesion, VCAM-1, and ICAM-1 expression in TNF-α-activated endothelial cells. Rotenone, cyclosporine A, and bongkrekic acid suppress TNF-α-induced VCAM-1 expression. Overexpression of PBR inhibits voltage-dependent anion channel-1 (VDAC-1) expression and the silencing of PBR increases VDAC-1 expression in endothelial cells...

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AIMS: Stress can cause adverse reactions in the body that induce a wide range of biochemical and behavioral changes. Oxidative damage is an established outcome of stress that has been implicated in the pathogenesis of mood and anxiety disorders. Anxiolytic drugs are widely prescribed to treat these conditions; however, no animal study has investigated the effect of benzodiazepines on the levels of intracellular reactive oxygen species (ROS) in the peripheral blood leukocytes of stressed mice...

BACKGROUND: GABA(A) receptors are members of the Cys-loop family of neurotransmitter receptors, proteins which are responsible for fast synaptic transmission, and are the site of action of wide range of drugs. Recent work has shown that Cys-loop receptors are present on immune cells, but their physiological roles and the effects of drugs that modify their function in the innate immune system are currently unclear. We are interested in how and why anaesthetics increase infections in intensive care patients; a serious problem as more than 50% of patients with severe sepsis will die...

BACKGROUND: Many new candidate pharmaceuticals designed to improve recovery after stroke have been proposed recently, but there are still too few molecular imaging methods capable to assess their efficacy. A hallmark of the inflammatory reaction that follows focal cerebral ischemia is overexpression of the mitochondrial peripheral benzodiazepine receptor/18 kDa translocator protein (PBR/TSPO) in the monocytic lineage and astrocytes. This overexpression can be imaged with positron emission tomography (PET) using PBR/TSPO-selective radioligands such as [(18)F]DPA-714...

OBJECTIVE: To critically evaluate the role of several notable 'pain pathways' in the fibromyalgia syndrome (FMS). METHODS: PubMed provided the data base for peer-reviewed basic and clinical science studies on musculoskele-tal and neuropathic pain mechanisms with a principal emphasis on critically appraising papers from 2002 to the present. RESULTS: FMS pharmacotherapy is more prevalent in clinical practice as our understanding of the cellular, molecular and pathophysiologic mechanisms contributing to widespread musculoskeletal and neuropathic pain has emerged...

Many studies showed that benzodiazepines could modulate immune responses through interaction with peripheral benzodiazepine receptors (PBRs) in immune cells but most of the studies were focused on monocytes and macrophages. In the present study, we revealed that diazepam, a mixed-type benzodiazepine, inhibited IFN-gamma production by human peripheral blood mononuclear cells (PBMCs) induced by anti-CD3 in dose-dependent manner. Flow cytometry analysis demonstrated that diazepam could inhibit the frequency of IFN-gamma-producing CD4(+) and CD8(+) T cells...

Focal cerebral ischemia leads to an inflammatory reaction involving an overexpression of the peripheral benzodiazepine receptor (PBR)/18-kDa translocator protein (TSPO) in the cerebral monocytic lineage (microglia and monocyte) and in astrocytes. Imaging of PBR/TSPO by positron emission tomography (PET) using radiolabeled ligands can document inflammatory processes induced by cerebral ischemia. We performed in vivo PET imaging with [(18)F]DPA-714 to determine the time course of PBR/TSPO expression over several days after induction of cerebral ischemia in rats...

Focal cerebral ischemia elicits strong inflammatory responses involving activation of resident microglia and recruitment of monocytes/macrophages. These cells express peripheral benzodiazepine receptors (PBRs) and can be visualized by positron emission tomography (PET) using [(11)C]PK11195 that selectively binds to PBRs. Earlier research suggests that transient ischemia in rats induces increased [(11)C]PK11195 binding within the infarct core. In this study, we investigated the expression of PBRs during permanent ischemia in rats...

UNLABELLED: Overexpression of the translocator protein, TSPO (18 kDa), formerly known as the peripheral benzodiazepine receptor, is a hallmark of activation of cells of monocytic lineage (microglia and macrophages) during neuroinflammation. Radiolabeling of TSPO ligands enables the detection of neuroinflammatory lesions by PET. Two new radioligands, (11)C-labeled N,N-diethyl-2-[2-(4-methoxyphenyl)-5,7-dimethylpyrazolo[1,5-alpha]pyrimidin-3-yl]acetamide (DPA-713) and (18)F-labeled N,N-diethyl-2-(2-(4-(2-fluoroethoxy)phenyl)-5,7-dimethylpyrazolo[1,5-alpha]pyrimidin-3-yl)acetamide (DPA-714), both belonging to the pyrazolopyrimidine class, were compared in vivo and in vitro using a rodent model of neuroinflammation...

BACKGROUND: Midazolam is widely used as an intravenous sedative. However, the role of midazolam on vascular endothelial activation is still unknown. The present study explores the action of midazolam on endothelial activation and its role to peripheral benzodiazepine receptor (PBR) in cultured human umbilical vein endothelial cells. METHODS: Intracellular localization of PBR in human umbilical vein endothelial cells was visualized with immunofluorescent staining...

AIMS: Microglia are involved in neurodegeneration, are prime targets for anti-inflammatory therapy and are potential biomarkers of disease progression. For example, positron emission tomography imaging employing radioligands for the mitochondrial translocator protein of 18 kDa (TSPO, formerly known as the peripheral benzodiazepine receptor) is being scrutinized to detect neuroinflammation in various diseases. TSPO is presumably present in activated microglia, but may be present in other neural cells...

Cytotoxic effects on neuronal as well as on immune cells have been reported for both typical and atypical antipsychotic drugs. We evaluated the effects of different concentrations of a typical (haloperidol) and two atypical (clozapine, olanzapine) antipsychotics on the survival of human neuronal (SH-SY5Y cells) and immune cells (U937 cells) by determining the metabolic activity after 24 h of incubation by the modified tetrazolium method. The dopaminergic neuroblastoma SH-SY5Y and the lymphoma U-937 cell line are well established models for in vitro investigations...