Search results for "Homeostasis"
showing 10 items of 630 documents
IL-23-mediated mononuclear phagocyte crosstalk protects mice from Citrobacter rodentium-induced colon immunopathology.
2014
Gut homeostasis and mucosal immune defense rely on the differential contributions of dendritic cells (DC) and macrophages. Here we show that colonic CX3CR1+ mononuclear phagocytes are critical inducers of the innate response to Citrobacter rodentium infection. Specifically, the absence of IL-23 expression in macrophages or CD11b+ DC results in the impairment of IL-22 production and in acute lethality. Highlighting immunopathology as a death cause, infected animals are rescued by the neutralization of IL-12 or IFNγ. Moreover, mice are also protected when the CD103+ CD11b− DC compartment is rendered deficient for IL-12 production. We show that IL-12 production by colonic CD103+ CD11b− DC is r…
TFIIH Operates through an Expanded Proximal Promoter To Fine-Tune c-myc Expression
2004
A continuous stream of activating and repressing signals is processed by the transcription complex paused at the promoter of the c-myc proto-oncogene. The general transcription factor IIH (TFIIH) is held at promoters prior to promoter escape and so is well situated to channel the input of activators and repressors to modulate c-myc expression. We have compared cells expressing only a mutated p89 (xeroderma pigmentosum complementation group B [XPB]), the largest TFIIH subunit, with the same cells functionally complemented with the wild-type protein (XPB/wt-p89). Here, we show structural, compositional, and functional differences in transcription complexes between XPB and XPB/wt-89 cells at t…
Endoplasmic Reticulum and Mitochondria: Independent Roles and Crosstalk in Fatty Liver Diseases and Hepatic Inflammation.
2015
Proper function of the endoplasmic reticulum (ER) and mitochondria is essential for cellular homeostasis and the regulation of metabolic pathways. Perturbation of their function has been linked to pathophysiological states, including metabolic and liver diseases. Fatty liver diseases are a major health problem whose prevalence is dramatically increasing, may be induced by several factors (mainly chronic alcohol consumption, drugs or metabolic alterations), and share common features as lipid deposition, inflammation, oxidative stress and progression to more severe clinical stages, such as fibrosis, cirrhosis or even hepatocellular carcinoma. Besides their independent contributions to metabol…
Energy regulatory signals and food reward.
2009
The hormones insulin, leptin, and ghrelin have been demonstrated to act in the central nervous system (CNS) as regulators of energy homeostasis, acting at medial hypothalamic sites. Here, we summarize research demonstrating that, in addition to direct homeostatic actions at the hypothalamus, CNS circuitry that subserves reward and is also a direct and indirect target for the action of these endocrine regulators of energy homeostasis. Specifically, insulin and leptin can decrease food reward behaviors and modulate the function of neurotransmitter systems and neural circuitry that mediate food reward, the midbrain dopamine (DA) and opioidergic pathways. Ghrelin can increase food reward behavi…
Epithelial NEMO links innate immunity to chronic intestinal inflammation
2007
Deregulation of intestinal immune responses seems to have a principal function in the pathogenesis of inflammatory bowel disease(1-4). The gut epithelium is critically involved in the maintenance of intestinal immune homeostasis-acting as a physical barrier separating luminal bacteria and immune cells, and also expressing antimicrobial peptides(3,5,6). However, the molecular mechanisms that control this function of gut epithelial cells are poorly understood. Here we show that the transcription factor NF kappa B, a master regulator of pro-inflammatory responses(7,8), functions in gut epithelial cells to control epithelial integrity and the interaction between the mucosal immune system and gu…
MIPPIE: the mouse integrated protein–protein interaction reference
2020
Abstract Cells operate and react to environmental signals thanks to a complex network of protein–protein interactions (PPIs), the malfunction of which can severely disrupt cellular homeostasis. As a result, mapping and analyzing protein networks are key to advancing our understanding of biological processes and diseases. An invaluable part of these endeavors has been the house mouse (Mus musculus), the mammalian model organism par excellence, which has provided insights into human biology and disorders. The importance of investigating PPI networks in the context of mouse prompted us to develop the Mouse Integrated Protein–Protein Interaction rEference (MIPPIE). MIPPIE inherits a robust infr…
Exercise as the master polypill of the 21st century for the prevention of cardiovascular disease
2015
To the Editor,The growing pandemic of cardiovascular diseases (CVD) has para-doxically paralleled advances in pharmacology, and CVD remains theleading cause of death worldwide. Therapeutic strategies aiming atcontrolling several CVD risk factors simultaneously in individualswithout evidence of CVD are expensive and difficult to implement.Thus, the development of fixed-dose drug combinations of antiplatelettogether with blood pressure (BP) and cholesterol-lowering drugs,i.e., polypills, is gaining attention to prevent CVD [1,2] and all-causemortality [3], even after an acute coronary syndrome [4]. Despite thepotential of polypills to increase adherence at a lower cost [5], peoplerandomized to …
Liver X receptor activation promotes polyunsaturated fatty acid synthesis in macrophages : relevance in the context of atherosclerosis
2015
Objective— Liver X receptors (LXRs) modulate cholesterol and fatty acid homeostasis as well as inflammation. This study aims to decipher the role of LXRs in the regulation of polyunsaturated fatty acid (PUFA) synthesis in macrophages in the context of atherosclerosis. Approach and Results— Transcriptomic analysis in human monocytes and macrophages was used to identify putative LXR target genes among enzymes involved in PUFA biosynthesis. In parallel, the consequences of LXR activation or LXR invalidation on PUFA synthesis and distribution were determined. Finally, we investigated the impact of LXR activation on PUFA metabolism in vivo in apolipoprotein E–deficient mice. mRNA levels of acyl…
The frequent stressor and mental health monitoring-paradigm: a proposal for the operationalization and measurement of resilience and the identificati…
2021
Resilience has been defined as the maintenance or quick recovery of mental health during and after times of adversity. How to operationalize resilience and to determine the factors and processes that lead to good long-term mental health outcomes in stressor-exposed individuals is a matter of ongoing debate and of critical importance for the advancement of the field. One of the biggest challenges for implementing an outcome-based definition of resilience in longitudinal observational study designs lies in the fact that real-life adversity is usually unpredictable and that its substantial qualitative as well as temporal variability between subjects often precludes defining circumscribed time …
Physiological Micromechanics of the Anterior Mitral Valve Leaflet
2011
An improved understanding of mitral valve (MV) function remains an important goal for determining mechanisms underlying valve disease and for developing novel therapies. Critical to heart valve tissue homeostasis is the valvular interstitial cells (VICs), which reside in the interstitium and maintain the extracellular matrix (ECM) through both protein synthesis and enzymatic degradation [1]. There is scant experimental data on the alterations of the MV fiber network reorganization as a function of load, which is critical for implementation of computational strategies that attempt to link this meso-micro scale phenomenon. The observed large scale deformations experienced by VICs could be imp…