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https://www.readbyqxmd.com/read/28314211/the-role-of-kupffer-cells-in-hepatic-diseases
#1
REVIEW
Peizhi Li, Kun He, Jinzheng Li, Zuojin Liu, Jianping Gong
Kupffer cells (KCs) constitute 80-90% of the tissue macrophages present in the body. Essential to innate and adaptive immunity, KCs are responsible for the swift containment and clearance of exogenous particulates and immunoreactive materials which are perceived as foreign and harmful to the body. Similar to other macrophages, KCs also sense endogenous molecular signals that may result from perturbed homeostasis of the host. KCs have been implicated in host defense and the pathogenesis of various hepatic diseases, including endotoxin tolerance, liver transplantation, nonalcoholic fatty liver disease, and alcoholic liver disease...
March 14, 2017: Molecular Immunology
https://www.readbyqxmd.com/read/28275139/the-cytokine-response-to-lipopolysaccharide-does-not-predict-the-host-response-to-infection
#2
Benjamin A Fensterheim, Yin Guo, Edward R Sherwood, Julia K Bohannon
The magnitude of the LPS-elicited cytokine response is commonly used to assess immune function in critically ill patients. A suppressed response, known as endotoxin tolerance, is associated with worse outcomes, yet endotoxin tolerance-inducing TLR4 ligands are known to protect animals from infection. Thus, it remains unknown whether the magnitude of the LPS-elicited cytokine response provides an accurate assessment of antimicrobial immunity. To address this, the ability of diverse TLR ligands to modify the LPS-elicited cytokine response and resistance to infection were assessed...
March 8, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28258715/human-macrophages-chronically-exposed-to-lps-can-be-reactivated-by-stimulation-with-mdp-to-acquire-an-antimicrobial-phenotype
#3
Silvia Guzmán-Beltrán, Martha Torres, Monserrat Arellano, Esmeralda Juárez
Macrophages are important in host defense and can differentiate into functionally distinct subsets named classically (M1) or alternatively (M2) activated. In several inflammatory disorders, macrophages become tolerized to prevent deleterious consequences. This tolerization reduces the ability of macrophages to respond to bacterial components (e.g., LPS) maintaining a low level of inflammation but compromising the ability of macrophages to mount an effective immune response during subsequent pathogen encounters...
February 21, 2017: Cellular Immunology
https://www.readbyqxmd.com/read/28256612/the-role-of-indoleamine-2-3-dioxygenase-aryl-hydrocarbon-receptor-pathway-in-the-tlr4-induced-tolerogenic-phenotype-in-human-dcs
#4
Fabián Salazar, Dennis Awuah, Ola H Negm, Farouk Shakib, Amir M Ghaemmaghami
A controlled inflammatory response is required for protection against infection, but persistent inflammation causes tissue damage. Dendritic cells (DCs) have a unique capacity to promote both inflammatory and anti-inflammatory processes. One key mechanism involved in DC-mediated immunosuppression is the expression of tryptophan-metabolizing enzyme indoleamine 2,3-dioxygenase (IDO). IDO has been implicated in diverse processes in health and disease but its role in endotoxin tolerance in human DCs is still controversial...
March 3, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28254553/chronic-unpredictable-stress-abrogates-the-endotoxin-tolerance-induced-by-repeated-peripheral-lps-challenge-via-the-tlr4-signaling-pathway
#5
Jingyi Yan, Jianing Bai, Chen Gao, Yanling Liang, Baohua Zhao, Yanqing Bian
Endotoxin tolerance is induced by exposure to a repeated LPS challenge. Stress can exacerbate LPS-induced inflammation in the mouse hippocampus. However, the effects of stress on endotoxin tolerance have not been elucidated. The present experiments were designed to assess whether tolerance could be induced in the hippocampus by intraperitoneal injection of LPS at a dose of 250μg/kg for 7days, to investigate the effects of chronic unpredictable stress (CUS) on LPS-induced tolerance, and to assess underlying mechanisms in male Kunming mice...
February 28, 2017: Neuroscience Letters
https://www.readbyqxmd.com/read/28189043/type-i-interferon-signalling-is-not-required-for-the-induction-of-endotoxin-tolerance
#6
Yalda Karimi, Sophie M Poznanski, Fatemeh Vahedi, Branson Chen, Marianne V Chew, Amanda J Lee, Ali A Ashkar
Endotoxin, or LPS tolerance, is an immunomodulatory mechanism that results in a significantly diminished response to secondary LPS exposure, which may serve to protect the host against endotoxic shock. Type I interferons (IFNs) are cytokines released upon LPS binding to TLR4 and have been shown to have immunomodulatory properties. Due to this regulatory function of type I IFN, we aimed to investigate the role of type I IFN signalling in LPS tolerance. Our data suggests that type I IFN does not play a role in LPS tolerance in vitro, as both wild type and IFNAR1(-/-) peritoneal macrophages showed reduced cytokine production after secondary LPS exposure...
February 8, 2017: Cytokine
https://www.readbyqxmd.com/read/28183447/acute-low-dose-endotoxin-treatment-results-in-improved-whole-body-glucose-homeostasis-in-mice
#7
Joseph R Stevens, Ryan P McMillan, Justin T Resendes, Shannon K Lloyd, Mostafa M Ali, Madlyn I Frisard, Stefan Hargett, Susanna R Keller, Matthew W Hulver
BACKGROUND: Obese individuals present with an increased inflammatory tone as compared to healthy, normal-weight individuals, which is associated with insulin resistance. One factor hypothesized to contribute to increased inflammation in obese and diabetic states is elevated blood endotoxin levels, a condition known as metabolic endotoxemia. In non-obese and insulin sensitive individuals, circulating endotoxin concentrations fluctuate over the course of the day with elevations in the post-prandial state that return to baseline levels in the post-absorptive state...
March 2017: Metabolism: Clinical and Experimental
https://www.readbyqxmd.com/read/28178176/nlrp12-inflammasome-expression-in-the-rat-brain-in-response-to-lps-during-morphine-tolerance
#8
Sulie L Chang, Wenfei Huang, Xin Mao, Sabroni Sarkar
Morphine, an effective but addictive analgesic, can profoundly affect the inflammatory response to pathogens, and long-term use can result in morphine tolerance. Inflammasomes are protein complexes involved in the inflammatory response. The nucleotide-binding oligomerization domain-like receptor (NLR) Family Pyrin Domain Containing (NLRP) 12 (NLRP12) inflammasome has been reported to have anti-inflammatory activity. In this study, we examined the expression of NLRP12 inflammasome related genes in the adult F344 rat brain in response to the bacterial endotoxin lipopolysaccharide (LPS) in the presence and absence of morphine tolerance...
February 6, 2017: Brain Sciences
https://www.readbyqxmd.com/read/28142300/dose-dependent-immunomodulating-effects-of-endotoxin-in-allergic-airway-inflammation
#9
Sudhir Kumar, Atin Adhikari
How very high exposure levels to endotoxin in a farming environment provide protection against respiratory allergic symptoms and low-to-moderate levels of endotoxin in urban homes promote allergic response is unclear. Dose-specific bacterial endotoxin or LPS-induced tolerance mechanisms can affect lung inflammations, coupled with the Th2 immune responses. Here, we explored the effects of intranasal exposure of LPS at two different doses (based on occupational exposures during handling of agricultural wastes) in OVA-sensitized allergic wild type (WT) and TLR4-KO mice, particularly, with respect to Th2 cytokines and Tregs level...
January 1, 2017: Innate Immunity
https://www.readbyqxmd.com/read/28132721/hepatic-interleukin-6-production-is-maintained-during-endotoxin-tolerance-and-facilitates-lipid-accumulation
#10
Anna Dembek, Stephan Laggai, Sonja M Kessler, Beate Czepukojc, Yvette Simon, Alexandra K Kiemer, Jessica Hoppstädter
Gut-derived bacterial endotoxins, such as lipopolysaccharide (LPS), contribute to the pathogenesis of steatosis and steatohepatitis by activating Kupffer cells, the resident liver macrophages. Exposure of macrophages to low doses of LPS causes hyporesponsiveness upon subsequent endotoxin challenge, a phenomenon termed endotoxin or LPS tolerance. In the present study, we aimed to examine whether LPS-induced lipid accumulation is affected by endotoxin tolerance. LPS pretreatment reduced the expression of proinflammatory mediators upon subsequent high-dose LPS treatment in murine livers...
January 20, 2017: Immunobiology
https://www.readbyqxmd.com/read/28121488/the-potential-role-of-an-endotoxin-tolerance-like-mechanism-for-the-anti-inflammatory-effect-of-spirulina-platensis-organic-extract-in-macrophages
#11
Tho X Pham, Young-Ki Park, Minkyung Bae, Ji-Young Lee
Endotoxin tolerance is a phenomenon where exposure of innate immune cells to lipopolysaccharide (LPS) induces a refractory state to subsequent endotoxin exposures. The goal of this study was to investigate if Spirulina platensis organic extract (SPE) induces an endotoxin tolerance-like state. We used splenocytes and peritoneal macrophages from C57BL/6J mice fed a high-fat/high-sucrose (HF/HS) control or a HF/HS diet containing 0.25% (w/w) SPE for 16 weeks for ex vivo LPS stimulation and endotoxin-tolerant (ET) macrophages to evaluate the effects of SPE on endotoxin tolerance...
March 2017: Journal of Medicinal Food
https://www.readbyqxmd.com/read/28115526/circulating-monocytes-exhibit-an-endotoxin-tolerance-status-after-acute-ischemic-stroke-mitochondrial-dna-as-a-putative-explanation-for-poststroke-infections
#12
Enrique Hernández-Jiménez, María Gutierrez-Fernández, Carolina Cubillos-Zapata, Laura Otero-Ortega, Berta Rodríguez-Frutos, Víctor Toledano, Patricia Martínez-Sánchez, Blanca Fuentes, Aníbal Varela-Serrano, José Avendaño-Ortiz, Alberto Blázquez, María Ángeles Mangas-Guijarro, Exuperio Díez-Tejedor, Eduardo López-Collazo
Patients with acute ischemic stroke (AIS) suffer from infections associated with mortality. The relevance of the innate immune system, and monocytes in particular, has emerged as an important factor in the evolution of these infections. The study enrolled 14 patients with AIS, without previous treatment, and 10 healthy controls. In the present study, we show that monocytes from patients with AIS exhibit a refractory state or endotoxin tolerance. The patients were unable to orchestrate an inflammatory response against LPS and expressed three factors reported to control the evolution of human monocytes into a refractory state: IL-1R-associated kinase-M, NFkB2/p100, and hypoxia-inducible factor-1α...
January 23, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28077574/platelet-activating-factor-mediates-endotoxin-tolerance-by-regulating-indoleamine-2-3-dioxygenase-dependent-expression-of-the-suppressor-of-cytokine-signaling-3
#13
Kyung Tae Noh, In Duk Jung, Gil Sun Cha, Myung-Kwan Han, Yeong-Min Park
Indoleamine 2,3-dioxygenase (IDO) mediates immune tolerance, and suppressor of cytokine signaling 3 (SOCS3) negatively regulates the JAK/STAT signal transduction pathway. We determined previously that platelet-activating factor (PAF) protects mice against LPS-induced endotoxic shock, but its detailed mechanism of action was unknown. We performed survival experiments in IDO(+/+) and IDO(-/-) mice using an LPS-induced endotoxemia model and rated organ injury (neutrophil infiltration and liver function). Using ELISA and Western blotting, we also investigated the mechanism of PAF-mediated endotoxin tolerance during endotoxemia...
February 24, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28060378/cd73-regulates-anti-inflammatory-signaling-between-apoptotic-cells-and-endotoxin-conditioned-tissue-macrophages
#14
Patrick S Murphy, Jing Wang, Samir P Bhagwat, Joshua C Munger, William J Janssen, Terry W Wright, Michael R Elliott
The phagocytosis of apoptotic cells (efferocytosis) shifts macrophages to an anti-inflammatory state through a set of still poorly understood soluble and cell-bound signals. Apoptosis is a common feature of inflamed tissues, and efferocytosis by tissue macrophages is thought to promote the resolution of inflammation. However, it is not clear how the exposure of tissue macrophages to inflammatory cues (e.g., PAMPs, DAMPs) in the early stages of inflammation affects immune outcomes of macrophage-apoptotic cell interactions occurring at later stages of inflammation...
March 2017: Cell Death and Differentiation
https://www.readbyqxmd.com/read/28054645/characterization-of-a-model-of-systemic-inflammation-in-humans-in-vivo-elicited-by-continuous-infusion-of-endotoxin
#15
D Kiers, R M Koch, L Hamers, J Gerretsen, E J M Thijs, L van Ede, N P Riksen, M Kox, P Pickkers
Investigating the systemic inflammatory response in patients with critical illness such as sepsis, trauma and burns is complicated due to uncertainties about the onset, duration and severity of the insult. Therefore, in vivo models of inflammation are essential to study the pathophysiology and to evaluate immunomodulatory therapies. Intravenous bolus administration of endotoxin to healthy volunteers is a well-established model of a short-lived systemic inflammatory response, characterized by increased plasma cytokine levels, flu-like symptoms and fever...
January 5, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28011933/epigenetic-and-transcriptional-regulation-of-irak-m-expression-in-macrophages
#16
Konstantina Lyroni, Andreas Patsalos, Maria G Daskalaki, Christina Doxaki, Birte Soennichsen, Mike Helms, Ioannis Liapis, Vassiliki Zacharioudaki, Sotirios C Kampranis, Christos Tsatsanis
During macrophage activation, expression of IL-1R-associated kinase (IRAK)-M is induced to suppress TLR-mediated responses and is a hallmark of endotoxin tolerance. Endotoxin tolerance requires tight regulation of genes occurring at the transcriptional and epigenetic levels. To identify novel regulators of IRAK-M, we used RAW 264.7 macrophages and performed a targeted RNA interference screen of genes encoding chromatin-modifying enzymes, signaling molecules, and transcription factors involved in macrophage activation...
December 23, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/27913794/tlr-ligands-but-not-modulators-of-histone-modifiers-can-induce-the-complex-immune-response-pattern-of-endotoxin-tolerance-in-mammary-epithelial-cells
#17
Juliane Günther, Wolfram Petzl, Holm Zerbe, Hans-Joachim Schuberth, Hans-Martin Seyfert
Excessive stimulation of the TLR4 axis through LPS reduces the expression of some cytokine genes in immune cells, while stimulating the expression of immune defense genes during a subsequent bacterial infection. This endotoxin tolerance (ET) is mediated via epigenetic mechanisms. Priming the udder of cows with LPS was shown to induce ET in mammary epithelial cells (MEC), thereby protecting the udder against reinfection for some time. Seeking alternatives to LPS priming we tried to elicit ET by priming MEC with either lipopeptide (Pam2CSK4) via the TLR2/6 axis or inhibitors of histone-modifying enzymes...
December 1, 2016: Innate Immunity
https://www.readbyqxmd.com/read/27888109/ephestia-kuehniella-tolerance-to-bacillus-thuringiensis-cry1aa-is-associated-with-reduced-oligomer-formation
#18
Maissa Chakroun, Sameh Sellami, Juan Ferré, Slim Tounsi, Souad Rouis
The basis of the different susceptibility of Ephestia kuehniella to the Cry1Aa and Cry1Ac δ-endotoxins from Bacillus thuringiensis kurstaki BNS3 was studied. Both toxins bound specifically to the BBMV of E. kuehniella. The result of the ligand blot showed that Cry1Ac bound to three putative receptors of about 100, 65 and 80 kDa and Cry1Aa interacted only with a 100 kDa protein. Pronase digestion of the BBMV-bound toxins was used to analyze the toxin insertion. Both toxins inserted into the BBMV as monomers however, a 14 kDa peptide of α4-α5 which correspond to the oligomeric form of this peptide was detected in case of Cry1Ac only...
January 22, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/27868366/effects-of-gemigliptin-a-dipeptidyl-peptidase-4-inhibitor-on-lipid-metabolism-and-endotoxemia-after-a-high-fat-meal-in-patients-with-type-2-diabetes
#19
Chang Ho Ahn, Eun Ky Kim, Se Hee Min, Tae Jung Oh, Young Min Cho
We aimed to investigate the effects of gemigliptin, a dipeptidyl peptidase-4 inhibitor, on postprandial lipoprotein levels and endotoxemia in a randomized, double-blind, placebo-controlled, crossover study. Ten people with type 2 diabetes mellitus (T2DM), inadequately controlled with oral antidiabetic medications and/or lifestyle modification, were randomized to gemigliptin or placebo for 4 weeks. At the end of each treatment phase, the study participants underwent a high-fat meal tolerance test and needle aspiration of abdominal subcutaneous adipose tissue...
March 2017: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/27859049/lipopolysaccharide-primed-heterotolerant-dendritic-cells-suppress-experimental-autoimmune-uveoretinitis-by-multiple-mechanisms
#20
Izabela P Klaska, Elizabeth Muckersie, Cristina Martin-Granados, Maria Christofi, John V Forrester
Exposure of bone-marrow-derived dendritic cells (BMDC) to high-dose ultrapure lipopolysaccharide for 24 hr (LPS-primed BMDC) enhances their potency in preventing inter-photoreceptor retinoid binding protein: complete Freund's adjuvant-induced experimental autoimmune uveoretinitis (EAU). LPS-primed BMDC are refractory to further exposure to LPS (= endotoxin tolerance), evidenced here by decreased phosphorylation of TANK-binding kinase 1, interferon regulatory factor 3 (IRF3), c-Jun N-terminal kinase and p38 mitogen-activated protein kinase as well as impaired nuclear translocation of nuclear factor κB (NF-κB) and IRF3, resulting in reduced tumour necrosis factor-α (TNF-α), interleukin-6 (IL-6), IL-12 and interferon-β secretion...
March 2017: Immunology
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