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endotoxin tolerance

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https://www.readbyqxmd.com/read/29658572/pkr-inhibition-mediates-endotoxin-tolerance-in-macrophages-through-inactivation-of-pi3k-akt-signaling
#1
Hailin Xu, Juan Chen, Xiang Si, Minying Chen, Fei Pei, Chunfang Qiu, Jianfeng Wu, Xiangdong Guan
Following long‑term exposure to endotoxins, macrophages enter an immunosuppressive state that renders them unable respond to subsequent exposures to endotoxin, a phenomenon that is termed 'endotoxin tolerance'. Endotoxin tolerance increases the risks of secondary infection and mortality in patients with sepsis. In endotoxin‑tolerant macrophages, the mixed variation of gene transcription is referred to as macrophage reprogramming. The mechanisms underlying macrophage reprogramming remain unclear at present...
April 11, 2018: Molecular Medicine Reports
https://www.readbyqxmd.com/read/29649324/a-low-dose-lipid-infusion-is-sufficient-to-induce-insulin-resistance-and-a-pro-inflammatory-response-in-human-subjects
#2
Hanyu Liang, Helen Lum, Andrea Alvarez, Jose de Jesus Garduno-Garcia, Benjamin J Daniel, Nicolas Musi
OBJECTIVE: The root cause behind the low-grade inflammatory state seen in insulin resistant (obesity and type 2 diabetes) states is unclear. Insulin resistant subjects have elevations in plasma free fatty acids (FFA), which are ligands for the pro-inflammatory toll-like receptor (TLR)4 pathway. We tested the hypothesis that an experimental elevation in plasma FFA (within physiological levels) in lean individuals would upregulate TLR4 and activate downstream pathways (e.g., MAPK) in circulating monocytes...
2018: PloS One
https://www.readbyqxmd.com/read/29627620/efficacy-safety-and-tolerability-of-lubiprostone-for-the-treatment-of-non-alcoholic-fatty-liver-disease-in-adult-patients-with-constipation-the-lubiprone-double-blind-randomised-placebo-controlled-study-design
#3
Takaomi Kessoku, Kento Imajo, Takashi Kobayashi, Yasushi Honda, Takayuki Kato, Yuji Ogawa, Wataru Tomeno, Shingo Kato, Takuma Higurashi, Masato Yoneda, Hiroyuki Kirikoshi, Kazuki Kubota, Masataka Taguri, Takeharu Yamanaka, Haruki Usuda, Koichiro Wada, Satoru Saito, Atsushi Nakajima
BACKGROUND: This paper reports the protocol of a randomised, double-blind, placebo-controlled study to test the efficacy, safety, and tolerability of lubiprostone (LUB) vs. placebo on suppressing gut permeability in non-alcoholic fatty liver disease (NAFLD) patients with constipation. NAFLD, including non-alcoholic steatohepatitis (NASH), is a common chronic liver disorder. Progression is associated with increased gut permeability and gut-derived endotoxins. Most NAFLD/NASH clinical trial drugs aim to improve liver function or systemic metabolism...
April 5, 2018: Contemporary Clinical Trials
https://www.readbyqxmd.com/read/29626604/transgenerational-effects-of-paternal-dietary-astragalus-polysaccharides-on-spleen-immunity-of-broilers
#4
Yulong Li, Xinyu Lei, Zhenchen Yin, Wei Guo, Shengru Wu, Xiaojun Yang
Our previous study indicated that paternal dietary Astragalus polysaccharides (APS) could induce endotoxin tolerance-like response in jejunum of offspring chickens. There exist positive interaction between intestinal mucosal immunity and systemic immunity. So we studied the transgenerational effect and nutri-epigenetic role of paternal dietary APS on spleen immunity. 64 one-day-old Avein breeder cocks were used in a single-factor design with 0 and 10 g/kg APS, respectively, 4 replicated cages each group, and 8 birds each cage...
April 4, 2018: International Journal of Biological Macromolecules
https://www.readbyqxmd.com/read/29619418/the-role-of-intestinal-c-type-regenerating-islet-derived-3-lectins-for-nonalcoholic-steatohepatitis
#5
Sena Bluemel, Lirui Wang, Cameron Martino, Suhan Lee, Yanhan Wang, Brandon Williams, Angela Horvath, Vanessa Stadlbauer, Karsten Zengler, Bernd Schnabl
C-type regenerating islet derived-3 (Reg3) lectins defend against pathogens and keep commensal bacteria at a distance. Deficiency of Reg3g and Reg3b facilitates alcohol-induced bacterial translocation and alcoholic liver disease. Intestinal Reg3g is down-regulated in animal models of diet-induced obesity, but the functional consequences for nonalcoholic steatohepatitis (NASH) are unknown. The aim of this study was to investigate the role of Reg3 lectins in NASH. NASH was induced by a Western-style fast-food diet in mice deficient for Reg3g or Reg3b and in transgenic mice overexpressing Reg3g in intestinal epithelial cells ( Reg3g Tg)...
April 2018: Hepatology Communications
https://www.readbyqxmd.com/read/29593712/mitochondrial-sirtuin-4-resolves-immune-tolerance-in-monocytes-by-rebalancing-glycolysis-and-glucose-oxidation-homeostasis
#6
Jie Tao, Jingpu Zhang, Yun Ling, Charles E McCall, Tie Fu Liu
The goal of this investigation was to define the molecular mechanism underlying physiologic conversion of immune tolerance to resolution of the acute inflammatory response, which is unknown. An example of this knowledge gap and its clinical importance is the broad-based energy deficit and immunometabolic paralysis in blood monocytes from non-survivors of human and mouse sepsis that precludes sepsis resolution. This immunometabolic dysregulation is biomarked by ex vivo endotoxin tolerance to increased glycolysis and TNF-α expression...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29582430/human-periodontal-ligament-cells-exhibit-no-endotoxin-tolerance-upon-stimulation-with-porphyromonas-gingivalis-lipopolysaccharide
#7
A Blufstein, C Behm, P Q Nguyen, X Rausch-Fan, O Andrukhov
BACKGROUND/OBJECTIVES: Endotoxin tolerance is characterized by a state of hyporesponsiveness after confrontation with endotoxins such as lipopolysaccharides (LPS) at low concentrations. The aim of this study was to investigate, whether pretreatment with Porphyromonas gingivalis leads to endotoxin tolerance induction and possible alterations in toll-like receptor (TLR) 2- and 4-induced response in human periodontal ligament cells (hPDLCs). MATERIAL AND METHODS: Primary hPDLCs were pretreated with P...
March 26, 2018: Journal of Periodontal Research
https://www.readbyqxmd.com/read/29563175/ifn-regulatory-factor-2-inhibits-expression-of-glycolytic-genes-and-lipopolysaccharide-induced-proinflammatory-responses-in-macrophages
#8
Huachun Cui, Sami Banerjee, Sijia Guo, Na Xie, Gang Liu
Rapid initiation and timely resolution of inflammatory response in macrophages are synergistic events that are known to be equally critical to optimal host defense against pathogen infections. However, the regulation of these processes, in particular by a specific cellular metabolic program, has not been well understood. In this study, we found that IFN regulatory factor 2 (IRF2) underwent an early degradation in a proteasome-mediated pathway in LPS-treated mouse macrophages, followed by a later recovery of the expression via transactivation...
March 21, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/29545322/the-role-of-heat-tolerant-endotoxin-retentive-ultrafilters-ufs-for-the-remediation-of-reverse-osmosis-ro-plants-employed-for-surgical-hand-antisepsis-using-periodic-thermal-disinfection-a-ten-year-longitudinal-experience-study-in-the-operating-theater
#9
Yushi Uetera, Hiroshi Yasuhara, Naohito Kumada, Yoshiki Misawa, Yoshiyuki Terada, Yoshio Satou, Tamaki Suhara, Kunio Kawamura
Recently, the use of filters has come into light for sanitizing water plants. This study investigated the role of heat-tolerant ultrafilters (UFs) for the remediation of reverse osmosis (RO) plants using periodic thermal disinfection. Two completely identical RO plants (RO plants A & B) were installed in 2006 for surgical hand antisepsis in the operating theater. RO water was stored in the 300-liter storage tank and re-circulated in the 190 meter-long loop delivering water to 12 faucets in each RO plant...
March 15, 2018: PDA Journal of Pharmaceutical Science and Technology
https://www.readbyqxmd.com/read/29510400/adam17-mediated-ectodomain-shedding-of-toll-like-receptor-4-as-a-negative-feedback-regulation-in-lipopolysaccharide-activated-aortic-endothelial-cells
#10
Won Seok Yang, Jin Ju Kim, Mee Jeong Lee, Eun Kyoung Lee, Su-Kil Park
BACKGROUND/AIMS: Lipopolysaccharide (LPS)-activated monocytes/macrophages develop endotoxin tolerance in part by reducing cell surface toll-like receptor 4 (TLR4) through cluster of differentiation 14 (CD14)-dependent endocytosis. In case of endothelial cells, CD14 is expressed in low copy numbers as compared with monocytes/macrophages. Thus, we explored how endothelial cells regulate TLR4 expression after LPS stimulation. METHODS: Cultured human aortic endothelial cells (HAECs) were treated with LPS...
February 28, 2018: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/29441948/regulation-and-mechanism-of-mir-146-on-renal-ischemia-reperfusion-injury
#11
Yuyu Huang, Hongwu Wang, Yanhui Wang, Xiaohui Peng, Jing Li, Wenlong Gu, Ting He, Minjun Chen
AIM: MicroRNAs (miRs) are endogenous substances that act as important diagnostic and treatment targets in renal diseases. miR-146 plays an important role in the development of endotoxin tolerance through NF-κB pathway, but the underlying mechanism is not clearly understood. The aim of this study was to determine the molecular regulation and function of miR-146 and also the expression of miR-146 in an experimental model of renal ischemia reperfusion injury (IRI). METHODS: IRI was induced in mouse by bilateral IRI for 45 min followed by reperfusion...
January 2, 2018: Die Pharmazie
https://www.readbyqxmd.com/read/29431864/negative-regulators-that-mediate-ocular-immune-privilege
#12
REVIEW
Andrew W Taylor, Tat Fong Ng
The ocular microenvironment has adapted several negative regulators of inflammation to maintain immune privilege and health of the visual axis. Several constitutively produced negative regulators within the eye TGF-β2, α-melanocyte stimulating hormone (α-MSH), Fas ligand (FasL), and PD-L1 standout because of their capacity to influence multiple pathways of inflammation, and that they are part of promoting immune tolerance. These regulators demonstrate the capacity of immune privilege to prevent the activation of inflammation, and to suppress activation of effector immune cells even under conditions of ocular inflammation induced by endotoxin and autoimmune disease...
February 12, 2018: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/29390039/serum-amyloid-a3-is-required-for-normal-weight-and-immunometabolic-function-in-mice
#13
Jennifer L Ather, Matthew E Poynter
Serum amyloid A (SAA) is an apolipoprotein that is robustly upregulated in numerous inflammatory diseases and has been implicated as a candidate pro-inflammatory mediator. However, studies comparing endogenous SAAs and recombinant forms of the acute phase protein have generated conflicting data on the function of SAA in immunity. We generated SAA3 knockout mice to evaluate the contribution of SAA3 to immune-mediated disease, and found that mice lacking SAA3 develop adult-onset obesity and metabolic dysfunction along with defects in innate immune development...
2018: PloS One
https://www.readbyqxmd.com/read/29355626/transgenerational-endotoxin-tolerance-like-effect-caused-by-paternal-dietary-astragalus-polysaccharides-in-broilers-jejunum
#14
Yulong Li, Xinyu Lei, Wei Guo, Shengru Wu, Yulan Duan, Xin Yang, Xiaojun Yang
To learn the nutri-epigenetics role of Astragalus polysaccharides (APS), we designed and studied the transgenerational effect of paternal dietary APS supplementation in chickens. 160 Avein breeder cocks were randomly allocated into 5 groups and fed with 0, 0.01, 0.1, 1, and 10 g/kg APS supplement, respectively. Sperm of breeder cocks was collected and used for hatching experiment to get broiler chickens when the cocks at 40-weeks-old. It showed that the paternal dietary 10 g/kg APS could transgenerational promote growth performance and jejunal tissue morphology of chickens...
May 2018: International Journal of Biological Macromolecules
https://www.readbyqxmd.com/read/29343645/crystal-structure-of-the-mammalian-lipopolysaccharide-detoxifier
#15
Alexei Gorelik, Katalin Illes, Bhushan Nagar
LPS is a potent bacterial endotoxin that triggers the innate immune system. Proper recognition of LPS by pattern-recognition receptors requires a full complement of typically six acyl chains in the lipid portion. Acyloxyacyl hydrolase (AOAH) is a host enzyme that removes secondary (acyloxyacyl-linked) fatty acids from LPS, rendering it immunologically inert. This activity is critical for recovery from immune tolerance that follows Gram-negative infection. To understand the molecular mechanism of AOAH function, we determined its crystal structure and its complex with LPS...
January 17, 2018: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29328416/endotoxin-tolerance-induced-by-lipopolysaccharide-preconditioning-protects-against-surgery%C3%A2-induced-cognitive-impairment-in-aging-mice
#16
Zhijie Zhang, Muhuo Ji, Yanlin Liao, Jianjun Yang, Jun Gao
Postoperative cognitive dysfunction (POCD) is a clinical syndrome characterized by varying degrees of cognitive functional decline in patients following major surgery. Inflammation and a dysregulated innate immune system exert broad effects in the periphery and central nervous system, yet the mechanisms underlying POCD remain poorly understood and without effective therapy. It has been reported that modulation of the dysregulated inflammatory response with low‑dose lipopolysaccharide (LPS) preconditioning, a phenomenon additionally referred to as endotoxin tolerance, has the potential to reduce neuroinflammation, blood‑brain barrier disruption, and cognitive impairment in a number of disease states...
March 2018: Molecular Medicine Reports
https://www.readbyqxmd.com/read/29251774/altered-toll-like-receptor-responsiveness-underlies-a-dominant-heritable-defect-in-b-cell-tolerance-in-autoimmune-new-zealand-black-mice
#17
Amy G Clark, Elizabeth S Buckley, Mary H Foster
Systemic lupus erythematosus is a debilitating autoimmune disease in which autoantibodies and autoreactive T cells destroy kidneys and other organs. Disease is clinically and genetically heterogeneous, suggesting that underlying mechanisms vary between patients. We previously used an autoantibody transgenic mouse reporter system to examine the effect of different autoimmune backgrounds on B-cell tolerance, failure of which is a fundamental defect in lupus. We identified a defect consistent with reversible anergy induced by endotoxin stimulation of B cells from Ig transgenic New Zealand Black (NZB) mice...
March 2018: European Journal of Immunology
https://www.readbyqxmd.com/read/29204141/-flos-lonicera-combined-with-metformin-ameliorates-hepatosteatosis-and-glucose-intolerance-in-association-with-gut-microbiota-modulation
#18
Na R Shin, Shambhunath Bose, Jing-Hua Wang, AbuZar Ansari, Soo-Kyoung Lim, Young-Won Chin, Han-Seok Choi, Hojun Kim
The gut microbiota is important in energy contribution, metabolism and immune modulation, and compositional disruption of the gut microbiota population is closely associated with chronic metabolic diseases like type 2 diabetes (T2D) and non-alcoholic fatty liver disease (NAFLD). Metformin (MET) and Flos Lonicera (FL) are common treatments for metabolic diseases in Western and Oriental medicinal fields. We evaluated the effect of treatment with FL and MET in combination on hepatosteatosis, glucose tolerance, and gut microbial composition...
2017: Frontiers in Microbiology
https://www.readbyqxmd.com/read/29166392/intestinal-ralstonia-pickettii-augments-glucose-intolerance-in-obesity
#19
Shanthadevi D Udayappan, Petia Kovatcheva-Datchary, Guido J Bakker, Stefan R Havik, Hilde Herrema, Patrice D Cani, Kristien E Bouter, Clara Belzer, Julia J Witjes, Anne Vrieze, Eleanore Susanne Victoria de Sonnaville, Alice Chaplin, Daniel H van Raalte, Steven Aalvink, Geesje M Dallinga-Thie, Hans G H J Heilig, Göran Bergström, Suzan van der Meij, Bart A van Wagensveld, Joost B L Hoekstra, Frits Holleman, Erik S G Stroes, Albert K Groen, Fredrik Bäckhed, Willem M de Vos, Max Nieuwdorp
An altered intestinal microbiota composition has been implicated in the pathogenesis of metabolic disease including obesity and type 2 diabetes mellitus (T2DM). Low grade inflammation, potentially initiated by the intestinal microbiota, has been suggested to be a driving force in the development of insulin resistance in obesity. Here, we report that bacterial DNA is present in mesenteric adipose tissue of obese but otherwise healthy human subjects. Pyrosequencing of bacterial 16S rRNA genes revealed that DNA from the Gram-negative species Ralstonia was most prevalent...
2017: PloS One
https://www.readbyqxmd.com/read/29154959/early-life-innate-immune-signatures-of-persistent-food-allergy
#20
Melanie R Neeland, Jennifer J Koplin, Thanh D Dang, Shyamali C Dharmage, Mimi L Tang, Susan L Prescott, Richard Saffery, David J Martino, Katrina J Allen
BACKGROUND: Food allergy naturally resolves in a proportion of food-allergic children without intervention; however the underlying mechanisms governing the persistence or resolution of food allergy in childhood are not understood. OBJECTIVES: This study aimed to define the innate immune profiles associated with egg allergy at age 1 year, determine the phenotypic changes that occur with the development of natural tolerance in childhood, and explore the relationship between early life innate immune function and serum vitamin D...
November 14, 2017: Journal of Allergy and Clinical Immunology
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