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https://www.readbyqxmd.com/read/27891130/molecular-mechanisms-that-underlie-the-dynamic-adaptation-of-innate-monocyte-memory-to-varying-stimulant-strength-of-tlr-ligands
#1
Ruoxi Yuan, Shuo Geng, Liwu Li
In adaptation to rising stimulant strength, innate monocytes can be dynamically programed to preferentially express either pro- or anti-inflammatory mediators. Such dynamic innate adaptation or programing may bear profound relevance in host health and disease. However, molecular mechanisms that govern innate adaptation to varying strength of stimulants are not well understood. Using lipopolysaccharide (LPS), the model stimulant of toll-like-receptor 4 (TLR4), we reported that the expressions of pro-inflammatory mediators are preferentially sustained in monocytes adapted by lower doses of LPS, and suppressed/tolerized in monocytes adapted by higher doses of LPS...
2016: Frontiers in Immunology
https://www.readbyqxmd.com/read/27888557/adoptive-transfer-of-t-regulatory-cells-inhibits-lipopolysaccharide-induced-inflammation-in-fetal-brain-tissue-in-a-late-pregnancy-preterm-birth-mouse-model
#2
Fan Wang, Mi Xiao, Ru-Juan Chen, Xiao-Jie Lin, Muhammad Siddiq, Li Liu
To evaluate the effect of regulatory T cells (Tregs) on the inflammation resulting from lipopolysaccharide (LPS) challenge in prenatal brain tissue, Tregs isolated from pregnant mice were transferred into model mice, and the expression levels of fork head family transcription factor (Foxp3), interleukin-6 (IL-6), CD68 (a marker of microglia), and toll-like receptor 4 (TLR-4) were assessed in the fetal brain tissue. Foxp3, IL-6 and TLR-4 expression were detected by polymerase chain reaction and western blot; CD68 expression level was detected using immunochemical analysis...
November 26, 2016: Cell Biology International
https://www.readbyqxmd.com/read/27884587/butyrate-pretreatment-attenuates-heart-depression-in-a-mice-model-of-endotoxin-induced-sepsis-via-anti-inflammation-and-anti-oxidation
#3
Fangyan Wang, Zengyou Jin, Kaiyi Shen, Tingting Weng, Zhisong Chen, Jiahui Feng, Zhengzheng Zhang, Jiaming Liu, Xiaolong Zhang, Maoping Chu
OBJECTIVES: The depressed heart function is the main complication to cause death of septic patients in clinic. It is urgent to find effective interventions for this intractable disease. In this study, we investigated whether butyrate could be protective for heart against sepsis and the underlying mechanism. METHODS: Mice were randomly divided into three groups. Model group challenged with LPS (30 mg/kg, i.p.) only. Butyrate group received butyrate (200 mg/kg·d) for 3days prior to LPS administration (30 mg/kg)...
November 11, 2016: American Journal of Emergency Medicine
https://www.readbyqxmd.com/read/27882694/fused-bicyclic-caspase-1-inhibitors-assembled-by-copper-free-strain-promoted-alkyne-azide-cycloaddition-spaac
#4
Linghui Qian, Chong-Jing Zhang, Ji'en Wu, Shao Q Yao
Challenges exist in the development of potent and selective small-molecule inhibitors against caspase-1. Herein, by making use of the copper-free strain-promoted alkyne-azide cycloaddition (SPAAC) reaction between difluorinated cyclooctynes (DIFOs) and various azide-containing compounds, we showed for the first time that potential caspase-1 inhibitors could be rapidly synthesized. The resulting fused bicyclic compounds structurally resembled the central portion (P2 -P3 ) of Pralnacasan (a well-known small molecule caspase-1 inhibitor), with diversity at the P4 -position of the parental inhibitor conveniently installed from the azide component...
November 24, 2016: Chemistry: a European Journal
https://www.readbyqxmd.com/read/27879415/the-angiotensin-converting-enzyme-inhibitor-captopril-rescues-mice-from-endotoxin-induced-lethal-hepatitis
#5
Pu Ge, Rong Jiang, Xin Yao, Jing Li, Jie Dai, Li Zhang, Bin Ye
The renin-angiotensin system is classically regarded as a crucial regulator of circulatory homeostasis, but recent studies also revealed its pro-inflammatory roles. The beneficial effects of the angiotensin-converting enzyme inhibitor (ACEI) in severe inflammatory injury in the lung and heart have been previously reported, but its potential effects on lethal hepatitis were unknown. In this study, a mouse model with LPS/d-galactosamine (GalN)-induced fulminant hepatitis were used to test the protective potential of captopril, a representative ACEI...
November 22, 2016: Innate Immunity
https://www.readbyqxmd.com/read/27864832/colistin-reduces-lps-triggered-inflammation-in-a-human-sepsis-model-in-vivo-a-randomized-controlled-trial
#6
Peter Matzneller, Sabine Strommer, Christa Drucker, Karin Petroczi, Christian Schörgenhofer, Edith Lackner, Bernd Jilma, Markus Zeitlinger
OBJECTIVES: The previously described anti-endotoxin effect of colistin was not investigated in humans yet. We performed a randomized, double-blind, placebo-controlled crossover trial to determine the degree of colistin-driven modulation of inflammatory response in blood of lipopolysaccharide (LPS) - challenged healthy volunteers in a human endotoxemia model. METHODS: After a single intravenous dose of 2.5 million IU colistin methanesulfonate, IL-6, IL-8, TNF-α and IL-1β concentrations as well as other biomarkers of inflammation such as C-reactive protein, differential leukocyte counts and body temperature were measured up to 24 hours post-dose...
November 19, 2016: Clinical Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/27856275/rnaseq-profiling-of-primary-microglia-and-astrocyte-cultures-in-near-term-ovine-fetus-a-glial-in-vivo-in-vitro-multi-hit-paradigm-in-large-mammalian-brain
#7
M Cortes, M Cao, H L Liu, P Burns, C Moore, G Fecteau, A Desrochers, L B Barreiro, J P Antel, M G Frasch
BACKGROUND: The chronically instrumented fetal sheep is a widely used animal model to study fetal brain development in health and disease, but no methods exist yet to interrogate dedicated brain cell populations to identify their molecular and genomic phenotype. For example, the molecular mechanisms whereby microglia or astrocytes contribute to inflammation in the brain remain incompletely understood. NEW METHOD: Here we present a protocol to derive primary pure microglial or astrocyte cultures from near-term fetal sheep brain, after the animals have been chronically instrumented and studied in vivo...
November 14, 2016: Journal of Neuroscience Methods
https://www.readbyqxmd.com/read/27848249/cystathionine-%C3%AE-lyase-deficiency-exacerbates-ccl4-induced-acute-hepatitis-and-fibrosis-in-the-mouse-liver
#8
Lei Ci, Xing Yu Yang, Xiao Wen Gu, Qing Li, Yang Guo, Zi Ping Zhou, Meng Jie Zhang, Jia Hao Shi, Hua Yang, Zhu Gang Wang, Jian Fei
AIMS: The present study examined the role of cystathionine γ-lyase (CSE) in CCl4- induced liver damage. RESULTS: A CSE gene knock-out and luciferase gene knock-in mouse model was constructed to study the function of CSE and trace its expression in living status. CCl4 or LPS markedly downregulated CSE expression in the liver of mice. CSE-deficient mice showed increased serum alanine aminotransferase and aspartate aminotransferase levels, and liver damage after CCl4 challenge, whereas albumin and endogenous H2S levels decreased significantly...
November 16, 2016: Antioxidants & Redox Signaling
https://www.readbyqxmd.com/read/27843506/promotion-of-nickel-ni-allergy-by-anamnestic-sensitization-with-a-bacterial-component-lipopolysaccharide-lps-in-mice
#9
Norimasa Adachi, Eiji Takayama, Makoto Adachi, Masako Mizuno-Kamiya, Harumi Kawaki, Hiroko Takeuchi, Shuri Kubo, Hajime Ishigami, Masakazu Kurachi, Nobuo Kondoh
BACKGROUND/OBJECTIVE: Lipopolysaccharides (LPS) promote allergic responses to nickel (Ni) both in the sensitization and elicitation steps. In this study, we examine the effect of pre-sensitization to LPS on the occurrence of Ni allergy using a mouse model. METHOD: A 100 mg of LPS was injected into C57BL/6J mice intraperitoneally (ip). Three weeks later, the mice were subsequently injected with 0.3 μ moles of nickel dichloride (NiCl2) and 100 μg of CpG-DNA, which acted as an adjuvant...
2016: Open Dentistry Journal
https://www.readbyqxmd.com/read/27831566/cysteine-cathepsins-control-hepatic-nf-%C3%AE%C2%BAb-dependent-inflammation-via-sirtuin-1-regulation
#10
Álvaro de Mingo, Estefanía de Gregorio, Anna Moles, Núria Tarrats, Anna Tutusaus, Anna Colell, Jose C Fernandez-Checa, Albert Morales, Montserrat Marí
Sirtuin-1 (SIRT1) regulates hepatic metabolism but its contribution to NF-κB-dependent inflammation has been overlooked. Cysteine cathepsins (Cathepsin B or S, CTSB/S) execute specific functions in physiological processes, such as protein degradation, having SIRT1 as a substrate. We investigated the roles of CTSB/S and SIRT1 in the regulation of hepatic inflammation using primary parenchymal and non-parenchymal hepatic cell types and cell lines. In all cells analyzed, CTSB/S inhibition reduces nuclear p65-NF-κB and κB-dependent gene expression after LPS or TNF through enhanced SIRT1 expression...
November 10, 2016: Cell Death & Disease
https://www.readbyqxmd.com/read/27815261/soluble-epoxide-hydrolase-deficiency-or-inhibition-enhances-murine-hypoxic-pulmonary-vasoconstriction-after-lipopolysaccharide-challenge
#11
Martin Wepler, Arkadi Beloiartsev, Mary D Buswell, Dipak Panigrahy, Rajeev Malhotra, Emmanuel S Buys, Peter Radermacher, Fumito Ichinose, Donald B Bloch, Warren M Zapol
RATIONALE: Hypoxic pulmonary vasoconstriction (HPV) is the response of the pulmonary vasculature to low levels of alveolar oxygen. HPV improves systemic arterial oxygenation by matching pulmonary perfusion to ventilation during alveolar hypoxia, and is impaired in lung diseases such as the acute respiratory distress syndrome (ARDS) and in experimental models of endotoxemia. Epoxyeicosatrienoic acids (EETs) are pulmonary vasoconstrictors, which are metabolized to less vasoactive dihydroxyeicosatrienoic acids (DHETs) by soluble epoxide hydrolase (sEH)...
November 4, 2016: American Journal of Physiology. Lung Cellular and Molecular Physiology
https://www.readbyqxmd.com/read/27799931/immunomodulatory-factors-galectin-9-and-interferon-gamma-synergize-to-induce-expression-of-rate-limiting-enzymes-of-the-kynurenine-pathway-in-the-mouse-hippocampus
#12
Alexandra K Brooks, Marcus A Lawson, Jennifer L Rytych, Kevin C Yu, Tiffany M Janda, Andrew J Steelman, Robert H McCusker
Elevated levels of circulating pro-inflammatory cytokines are associated with symptomology of several psychiatric disorders, notably major depressive disorder. Symptomology has been linked to inflammation/cytokine-dependent induction of the Kynurenine Pathway. Galectins, like pro-inflammatory cytokines, play a role in neuroinflammation and the pathogenesis of several neurological disorders but without a clearly defined mechanism of action. Their involvement in the Kynurenine Pathway has not been investigated...
2016: Frontiers in Immunology
https://www.readbyqxmd.com/read/27799334/distinct-roles-of-integrins-%C3%AE-x%C3%AE-2-and-%C3%AE-m%C3%AE-2-on-leukocyte-subpopulations-during-inflammation-and-antimicrobial-responses
#13
Samir Jawhara, Elzbieta Pluskota, Wei Cao, Edward F Plow, Dmitry A Soloviev
Integrins αMβ2 and αXβ2 are homologous adhesive receptors that are expressed on many of the same leukocyte populations and bind many of the same ligands. Although αMβ2 was extensively characterized and implicated in leukocyte inflammatory and immune functions, the roles of αXβ2 remain largely obscure. Here, we tested the ability of mice deficient in integrins αMβ2 or αXβ2 to deal with opportunistic infections and the capacity of cells derived from these animals to execute inflammatory functions...
October 31, 2016: Infection and Immunity
https://www.readbyqxmd.com/read/27795394/outer-membrane-vesicle-production-facilitates-lps-remodeling-and-outer-membrane-maintenance-in-salmonella-during-environmental-transitions
#14
Katherine E Bonnington, Meta J Kuehn
: The ability of Gram-negative bacteria to carefully modulate outer membrane (OM) composition is essential to their survival. However, the asymmetric and heterogeneous structure of the Gram-negative OM poses unique challenges to the cell's successful adaption to rapid environmental transitions. Although mechanisms to recycle and degrade OM phospholipid material exist, there is no known mechanism by which to remove unfavorable lipopolysaccharide (LPS) glycoforms, except slow dilution through cell growth...
October 18, 2016: MBio
https://www.readbyqxmd.com/read/27794168/cd46-accelerates-macrophage-mediated-host-susceptibility-to-meningococcal-sepsis-in-a-murine-model
#15
Xiao Wang, Ding Zhang, Mikael Sjölinder, Yi Wan, Hong Sjölinder
CD46, a membrane cofactor expressed on all nucleated human cells, plays an essential role in suppressing autoimmune reactions and protecting host cells from complement-mediated attack. Human transgenic CD46 homozygous mice (CD46(+/+) ) are prone to lethal sepsis upon infection with Neisseria meningitidis (N. meningitidis). However, the underlying mechanisms are poorly understood. Here, we determined that CD46(+/+) mice produce large numbers of M1 type macrophages with enhanced surface expression of MHC II and production of pro-inflammatory mediators such as IL-6, TNF, IL-12, and IL-1β In the presence of M-CSF or GM-CSF, CD46 signaling enhances monocyte-macrophage differentiation...
October 28, 2016: European Journal of Immunology
https://www.readbyqxmd.com/read/27793136/activation-of-innate-immune-genes-in-caprine-blood-leukocytes-after-systemic-endotoxin-challenge
#16
Øyvind Salvesen, Malin R Reiten, Peter M H Heegaard, Michael A Tranulis, Arild Espenes, Kerstin Skovgaard, Cecilie Ersdal
BACKGROUND: Sepsis is a serious health problem associated with a range of infectious diseases in animals and humans. Early events of this syndrome can be mimicked by experimental administration of lipopolysaccharides (LPS). Compared with mice, small ruminants and humans are highly sensitive to LPS, making goats valuable in inflammatory models. We performed a longitudinal study in eight Norwegian dairy goats that received LPS (0.1 μg/kg, Escherichia coli O26:B6) intravenously. A control group of five goats received corresponding volumes of sterile saline...
October 28, 2016: BMC Veterinary Research
https://www.readbyqxmd.com/read/27790135/nox-2-mediated-phenotype-loss-of-hippocampal-parvalbumin-interneurons-might-contribute-to-postoperative-cognitive-decline-in-aging-mice
#17
Li-Li Qiu, Dan Luo, Hui Zhang, Yun S Shi, Yan-Jun Li, Dan Wu, Jiang Chen, Mu-Huo Ji, Jian-Jun Yang
Postoperative cognitive decline (POCD) is a common complication following anesthesia and surgery, especially in elderly patients; however, the precise mechanisms of POCD remain unclear. Here, we investigated whether nicotinamide adenine dinucleotide phosphate (NADPH) oxidase mediated-abnormalities in parvalbumin (PV) interneurons play an important role in the pathophysiology of POCD. The animal model was established using isoflurane anesthesia and exploratory laparotomy in 16-month-old male C57BL/6 mice. For interventional experiments, mice were chronically treated with the NADPH oxidase inhibitor apocynin (APO)...
2016: Frontiers in Aging Neuroscience
https://www.readbyqxmd.com/read/27785697/inhibition-of-lipopolysaccharide-induced-interleukin-8-in-human-adenocarcinoma-cell-line-ht-29-by-spore-probiotics-b-coagulans-and-b-subtilis-natto
#18
Masoumeh Azimirad, Masoud Alebouyeh, Tahereh Naji
Probiotics are used as a treatment for different intestinal disorders. They confer health benefits by different ways. This study was aimed to investigate immunomodulatory effect of Bacillus probiotic spores on the production of lipopolysaccharide (LPS)-induced interleukin 8 (IL-8) in HT-29 intestinal epithelial cells. Differentiated intestinal epithelial cell line was used as a model for the study of colonization of purified spores (Bacillus subtilis (natto) and B. coagulans) and their anti-inflammatory effects...
October 26, 2016: Probiotics and Antimicrobial Proteins
https://www.readbyqxmd.com/read/27782292/n-n-dimethylacetamide-significantly-attenuates-lps-and-tnf%C3%AE-induced-proinflammatory-responses-via-inhibition-of-the-nuclear-factor-kappa-b-pathway
#19
Ryan Pekson, Vladimir Poltoratsky, Samir Gorasiya, Sruthi Sundaram, Charles R Ashby, Ivana Vancurova, Sandra E Reznik
Previously, we have shown that N,N-dimethylacetamide (DMA) prevents inflammation-induced preterm birth in a murine model, inhibits LPS-induced increases in placental pro-inflammatory cytokines and up-regulates the anti-inflammatory cytokine Interleukin-10 (IL-10). However, DMA's mechanism of action remains to be elucidated. In the current study we investigate how DMA produces its anti-inflammatory effect. Using in vitro and ex vivo models, we show that DMA suppresses secretion of pro-inflammatory cytokines in lipopolysaccharide (LPS)-induced RAW 264...
October 24, 2016: Molecular Medicine
https://www.readbyqxmd.com/read/27780229/a-comparison-of-human-neutrophils-acquired-from-four-experimental-models-of-inflammation
#20
Alexander A Maini, Marc J George, Madhur P Motwani, Richard M Day, Derek W Gilroy, Alastair J O'Brien
Defects in neutrophil function have been implicated in a wide spectrum of clinical conditions. Several models are employed to study activated human neutrophils akin to those found at a site of inflammation. These include whole blood (WB) ex vivo stimulation with lipopolysaccharide (LPS) and in vivo techniques: cantharidin blister, skin windows and intra-dermal injection of UV-killed E.coli (UVKEc). Neutrophils obtained from these have never been compared. We compared the activation status of neutrophils from each technique in order to inform the optimal model for use in human studies...
2016: PloS One
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