Search results for "macrophage"
showing 10 items of 781 documents
Peritoneal Cavity is a Route for Gut-Derived Microbial Signals to Promote Autoimmunity in Non-Obese Diabetic Mice
2015
Macrophages play a crucial role in innate immune reactions, and peritoneal macrophages (PMs) guard the sterility of this compartment mainly against microbial threat from the gut. Type 1 diabetes (T1D) is an autoimmune disease in which gut microbiota and gut immune system appear to contribute to disease pathogenesis. We have recently reported elevated free radical production and increased permeability of gut epithelium in non-obese diabetic (NOD) mice. Impaired barrier function could lead to bacterial leakage to the peritoneal cavity. To explore the consequences of impaired gut barrier function on extra-intestinal immune regulation, we characterized peritoneal lavage cells from young newly w…
Oxidative stress protection by manganese complexes of tail-tied aza-scorpiand ligands.
2015
The Mn2+ coordination chemistry of double scorpiand ligands in which two polyazacyclophane macrocycles have been connected by pyridine, phenanthroline and bipyridine spacers has been studied by potentiometry, paramagnetic NMR and electrochemistry. All ligands show high stability with Mn2+ and the complexes were formed in a wide pH range. DFT calculations support the structures and coordination geometries derived from the study. A remarkable antioxidant activity was evidenced for these systems by the McCord-Fridovich assay and in Escherichiacoli sodAsodB deficient bacterial cells. The three systems were tested as anti-inflammatory drugs in human macrophages measuring the accumulation of cyto…
Does unsaponifiable fraction of grape seed oil attenuate nitric oxide production, oxidant and cytotoxicity activities.
2019
Triterpenoids, tocopherols, and phytosterols presented in unsaponifiable fraction of grape seed oil have several beneficial effects comprising antioxidant, anti-inflammatory, and antitumor capacities. In this study, the unsaponifiable fraction of three Tunisian grape seed varieties (Vitis vinifera L.), namely Merlot, Carignan, and Syrah, was investigated. The identified compounds were two triterpenic compounds (β-amyrin, lanosterol), six phytosterols (campesterol, ∆7 -avenasterol, stigmasterol, β-sitosterol, β-sitostanol, cholesterol), and three tocopherols (α, β, and γ tocopherols). The unsaponifiable fraction had significant protection against oxidative damage by modulating NO production …
Inhibition of endocannabinoid-degrading enzyme fatty acid amide hydrolase increases atherosclerotic plaque vulnerability in mice
2013
The role of endocannabinoids such as anandamide during atherogenesis remains largely unknown. Fatty acid amide hydrolase (FAAH) represents the key enzyme in anandamide degradation, and its inhibition is associated with subsequent higher levels of anandamide. Here, we tested whether selective inhibition of FAAH influences the progression of atherosclerosis in mice. Selective inhibition of FAAH using URB597 resulted in significantly increased plasma levels of anandamide compared to control, as assessed by mass spectrometry experiments in mice. Apolipoprotein E-deficient (ApoE(-/-)) mice were fed a high-fat, cholesterol-rich diet to induce atherosclerotic conditions. Simultaneously, mice recei…
Knock-down of the oxysterol receptor LXRα impairs cholesterol efflux in human primary macrophages: lack of compensation by LXRβ activation.
2012
Liver X Receptors (LXRs) α and β are oxysterol-activated nuclear receptors involved in the control of lipid metabolism and inflammation. Pharmacological activation of LXR is promising in the treatment of atherosclerosis since it can promote cholesterol efflux from macrophages and prevent foam cell formation. However, the development of LXR agonists has been limited by undesirable side-effects such as hepatic steatosis mediated by LXRα activation. Therefore, it has been proposed that targeting LXRα activators to extrahepatic tissues or using LXRβ-specific activators could be used as alternative strategies. It is not clear whether these molecules will retain the full atheroprotective potentia…
Reduced VLDL clearance in ApoeNpc1 mice is associated with increased Pcsk9 and Idol expression and decreased hepatic LDL-receptor levels
2010
Niemann-Pick type C1 (NPC1) promotes the transport of LDL receptor (LDL-R)-derived cholesterol from late endosomes/lysosomes to other cellular compartments. NPC1-deficient cells showed impaired regulation of liver_X receptor (LXR) and sterol regulatory element-binding protein (SREBP) target genes. We observed that Apoe(-/-)Npc1(-/-) mice displayed a marked increase in total plasma cholesterol mainly due to increased VLDL, reflecting decreased clearance. Although nuclear SREBP-2 and Ldlr mRNA levels were increased in Apoe(-/-)Npc1(-/-) liver, LDL-R protein levels were decreased in association with marked induction of proprotein convertase subtilisin/kexin type 9 (Pcsk9) and inducible degrade…
Polyamines Impair Immunity to Helicobacter pylori by Inhibiting L-Arginine Uptake Required for Nitric Oxide Production
2010
International audience; BACKGROUND & AIMS: Helicobacter pylori-induced immune responses fail to eradicate the bacterium. Nitric oxide (NO) can kill H pylori. However, translation of inducible NO synthase (iNOS) and NO generation by H pylori-stimulated macrophages is inhibited by the polyamine spermine derived from ornithine decarboxylase (ODC), and is dependent on availability of the iNOS substrate L-arginine (L-Arg). We determined if spermine inhibits iNOS-mediated immunity by reducing L-Arg uptake into macrophages. METHODS: Levels of the inducible cationic amino acid transporter (CAT) 2, ODC, and iNOS were measured in macrophages and H pylori gastritis tissues. L-Arg uptake, iNOS expressi…
Atherogenic properties of enzymatically degraded LDL: selective induction of MCP-1 and cytotoxic effects on human macrophages.
1998
Abstract —The mechanisms underlying the selective accumulation of macrophages in early atherosclerotic lesions are poorly understood but are likely to be related to specific properties of altered low density lipoprotein (LDL) deposited in the subendothelium. Enzymatic, nonoxidative degradation of LDL converts the lipoprotein to a potentially atherogenic moiety, enzymatically altered LDL (E-LDL), which activates complement and is rapidly taken up by human macrophages via a scavenger receptor–dependent pathway. Immunohistological evidence indicates that E-LDL is present in an extracellular location in the early lesion. We report that E-LDL causes massive release of monocyte chemotactic prote…
Complement and atherogenesis: The unknown connection
1999
The question why low-density lipoprotein (LDL) stranded in the subendothelium of arteries should acquire the proinflammatory properties that initiate and sustain atherogenesis has puzzled researchers for decades. The most popular concept contends that oxidative processes are crucial because oxidized LDL (ox-LDL) produced in vitro has atherogenic properties and small amounts of it are found in atherosclerotic lesions. Recently, a possible role for vascular infections has also been considered because infectious agents, in particular Chlamydia pneumoniae, are sometimes present in the lesions. Here, evidence is summarized for a different concept of atherogenesis, which evolves from the fact tha…
Modulation of dendritic cells and macrophages : implication in cancer and atherosclerosis
2010
During my thesis, I studied the cytotoxic function of dendritic cells (DC) from cancer patients and compared it to DC from healthy donors. Our results indicate that human monocyte-derived DC can acquire strong cytotoxic activity toward tumor cells after activation with low dose of LPS. The cytotoxic potential of DC derived from cancer patients was almost the same as the one generated from healthy donors. We identified the tumor cell killing mechanism which involves peroxynitrite release. After killing of cancer cells, DC are capable of engulfing dead tumor cell fragments and overexpress the costimulatory molecules necessary for T cell proliferation. A second study consisted in an analysis o…