Project description:Macrophage balance is important in several diseases. Raw 264.7 is a macrophage cell line. We previous detected that sialin (encoded by Slc17a5) play a key role in modulation of Raw264.7 which induced by LPS&IFNγ(M1 cells, proinflammatory cells) or IL4(M2 cells,anti-proinflammatory cells). Results showed nitrate could decrease the pro-inflammatory Raw264.7 cells while increase anti-inflammatory Raw26.7 cells. We transfected sialin overexpression plasmid to Raw264.7 and found that sialin could directly modulates Raw264.7 without nitrate. In this study, we want to figure out which genes could be the key factor modulated by sialin.
Project description:Although nonalcoholic fatty liver disease (NAFLD) is one of the leading causes of liver disease worldwide, no efficient treatment has been approved yet. We investigated whether oral nitrate administration prevents development of diet-induced NAFLD in two mouse models. Nitrate exerted its protective effect mainly through rebalancing of pro- and anti-inflammatory bone marrow monocyte–derived macrophages (MoMFs) in the liver. Using an NAFLD model in relatively germ-free mice and bone marrow–transplanted mice with a heritable Slc17a5 mutation, we showed that nitrate can prevent NAFLD by direct regulation of MoMFs through sialin, besides via the classical nitric oxide pathway. In vitro studies revealed that nitrate directly regulates mouse and human macrophages through the sialin-Sema4A pathway. Our work demonstrated for the first time nitrate’s ability to prevent NAFLD by directly modulating the homeostasis of hepatic pro- and anti-inflammatory macrophages, which indicates a novel strategy for potential clinical application in NAFLD.
Project description:bra-inra09-02_bioen_nitrogen - nitrate induction - nlp mutants - Short term nitrate induction kinetics in wildtype, nlp7-1, nlp7-3 and nlp6nlp7 - 10 days old seedling grown in liquid culture on 3mM nitrate wer starvec for N for 3 days and the kinetic for the resupply of nitrate was studied during a short kinetic (0,5, 10,20 minutes).
Project description:ngs2018_11_nlp2-no treatment / nitrate starvation / nitrate induction-Is NLP2 involved in the PNR Nitrate starvation and nitrate induction effects on wild type and mutant nlp2
Project description:Methotrexate (MTX) is an effectively used drug for certain forms of cancer and autoimmune diseases. However, its hepatotoxicity severely limits its clinical use which has no effective treatment but withdrawal. Therefore, further study is required to combat the liver injury associated with MTX. Nitrate, abundant in green vegetables, possesses diverse physiological roles including anti-inflammatory, antioxidant, and immunoregulation. This study investigated the preventive effect of nitrate on MTX-induced liver injury. The liver injury model in mice was induced by a single dose of MTX (20 mg/kg) injected intraperitoneally (i.p.). Administration of 2 mM nitrate in drinking water 5 days prior effectively mitigated MTX-elevated serum aminotransferases, attenuated hepatic pathological injury, reduced the level of hepatic apoptosis, and restored the proliferative capacity of hepatocytes. The molecular mechanism may involve the activation of the Wnt/β-catenin pathway. In this study, the hepatoprotective effect of nitrate on drug-induced liver injury (DILI) was identified for the first time, which provides a new idea for the prevention of drug-induced liver injury in clinical practice.
Project description:Recent research has shed light on the neuroimmunomodulation of macrophages, but the precise underlying mechanisms remain poorly understood.The maintenance of homeostasis in various organizations requires neuroimmune communication between the sympathetic nervous system and the immune system. The sympathetic nervous system adjusts macrophage phenotype via the adrenergic pathway.This study aimed to delineate the molecular mechanisms linking adrenergic pathway to RAW264.7.
Project description:The purpose of this study is to determine whether dietary nitrate supplementation improves performance in cardiopulmonary exercise testing (CPET).