Beneficial effects of curtailing immune susceptibility in an Alzheimer's disease model.

Background: Currently, there are no effective therapeutic options for Alzheimer's disease, the most common, multifactorial form of dementia, characterized by anomalous amyloid accumulation in the brain. Growing evidence points to neuroinflammation as a major promoter of AD. We have previously shown that the proinflammatory cytokine TNFSF10 fuels AD neuroinflammation, and that its immunoneutralization results in improved cognition in the 3xTg-AD mouse.

Tumor necrosis factor-related apoptosis-inducing ligand reduces the expression of the neuroprotective Na /Ca exchanger isoform NCX3 in human neuroblastoma SH-SY5Y cells.

Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), a cytokine belonging to the TNF superfamily, is regarded as a mediator of neurotoxicity. The constitutively expressed ion exchanger Na /Ca exchanger isoform-3 (NCX3) has been shown to protect neurons from injury. Its expression is induced by nerve growth factor (NGF) through activation of its tyrosine kinase receptor trkA.

Redundant modulatory effects of proinflammatory cytokines in human osteoblastic cells in vitro.

Objectives: The aim of our study was to investigate possible interaction of IL-17, TRAIL, and TNF-α in the modulation of osteoblast homeostasis in vitro, using human differentiated osteoblastic Saos-2 cells as in vitro model.

Methods: The effects of these cytokines on osteoblastic cell viability were assessed, by MTT assay, alone or in combination, at different times and concentrations. The effects of IL-17 and TNF-α on the regulatory system of osteoclast activity RANK/RANKL/ OPG were evaluated by Western blot and ELISA techniques in cell culture media.

The Proinflammatory Cytokine GITRL Contributes to TRAIL-mediated Neurotoxicity in the HCN-2 Human Neuronal Cell Line.

Background: Cytokines belonging to the TNF superfamily play a relevant role in neurodegenerative processes. Tumor Necrosis Factor-Related Apoptosis-Inducing Ligand (TRAIL), released during neuronal injury, has proven to potently mediate and sustain neurotoxic processes leading to neuronal death. Similarly to TRAIL, the cytokine Glucocorticoid-induced TNF receptor ligand (GITRL) is able to transduce proapoptotic signals.

The antimitogenic effect of the cannabinoid receptor agonist WIN55212-2 on human melanoma cells is mediated by the membrane lipid raft.

Here are reported the antiproliferative effects of the cannabinoid agonist WIN upon human melanoma cells expressing mRNA and protein for both CB1 and CB2 receptors. While WIN exerted antimitogenic effects, selective CB1 or CB2 agonists were unable to reproduce such effects and selective CB1 and CB2 antagonists did not inhibit WIN-induced cell death. Cells treated with WIN, preincubated with the lipid raft disruptor methylcyclodestrin, were rescued from death.

Endocannabinoids inhibit release of nerve growth factor by inflammation-activated mast cells.

Nerve growth factor (NGF) is a pleiotropic member of the neurotrophin family. Beside its neuronal effects, NGF plays a role in various processes, including angiogenesis. Mast cells release NGF and are among elements contributing to angiogenesis, a process regulated by arrays of factors, including the inhibitory cannabinoids.

The role of antioxidant supplement in immune system, neoplastic, and neurodegenerative disorders: a point of view for an assessment of the risk/benefit profile.

This review will discuss some issues related to the risk/benefit profile of the use of dietary antioxidants. Thus, recent progress regarding the potential benefit of dietary antioxidants in the treatment of chronic diseases with a special focus on immune system and neurodegenerative disorders will be discussed here. It is well established that reactive oxygen species (ROS) play an important role in the etiology of numerous diseases, such as atherosclerosis, diabetes and cancer.

Protective effects of the sigma agonist Pre-084 in the rat retina.

Aim: With the rationale that amyloid beta (AB) is toxic to the retina, we here assessed the role of TRAIL, a mediator of AB toxicity and related signal transduction, in a rat model. We also attempted to demonstrate possible protective effects of sigma 1 receptor agonists in these processes.

Methods: AB and the sigma 1 receptor agonist Pre-084 were injected intravitreally in the anaesthetised rat.

Protective effects of amylin on reserpine-induced gastric damage in the rat.

Here we show that the vasoactive peptide amylin protects against reserpine-induced gastric injury in the rat, resulting in lower score of gastric lesions. Hepatocyte growth factor (HGF), its c-Met receptor and cyclooxygenase-2 (COX-2) expression, usually increased in course of reserpine-induced gastric damage, was decreased in rats treated with amylin. Pretreatment with the specific amylin receptor antagonist AC187 abrogated the gastroprotective effects of amylin and restored high expression levels of HGF, c-Met and COX-2.

Trail interacts redundantly with nitric oxide in rat astrocytes: potential contribution to neurodegenerative processes.

The proapoptotic cytokine TRAIL has been shown to enhance amyloid-beta-dependent neurotoxicity. Here are reported interactions between TRAIL and nitric oxide (NO) in cultured rat astrocytes in vitro. Rat astrocytes expressed all TRAIL receptor mRNAs and proteins.

Effect of adrenomedullin on c-Met receptor expression after reserpine-induced gastric damage in the rat.

Here, we show an increase in c-Met receptor expression during reserpine-induced gastric damage in the rat, as assessed by immunohistochemistry. Pretreatment of animals with adrenomedullin prevented this increase in c-Met expression. c-Met immunoreactivity was localized in gastric glands.

Growth hormone protects human lymphocytes from irradiation-induced cell death.

1. Undesired effects of cancer radiotherapy mainly affect the hematopoietic system. Growth hormone (GH) participates in both hematopoiesis and modulation of the immune response.

Nerve growth factor-endothelial cell interaction leads to angiogenesis in vitro and in vivo.

Nerve growth factor (NGF) has important functions during embryonic development and on various tissues and organs under normal and pathological conditions during the extrauterine life. RT-PCR analysis and immunological methods demonstrate that human umbilical vein endothelial cells (HUVECs) express the NGF receptors trkA(NGFR) and p75NTR. NGF treatment caused a rapid phosphorylation of trkA(NGFR) in HUVECs, determining a parallel increase of phosphorylated ERK1/2.

Gastroprotective effect of adrenomedullin administered subcutaneously in the rat.

Subcutaneous injections of adrenomedullin prevented reserpine-induced gastric mucosal damage in a dose-dependent manner (1-1000 ng/kg), but did not interfere with the lesions produced by ethanol administration. In pylorus-ligated rats adrenomedullin significantly reduced gastric volume, total and free acid output as well as ulcer formation. The gastroprotective activity of adrenomedullin was not present in rats pretreated with cysteamine.