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Lps challenge model

Akbar Ahmad, Domokos Gerö, Gabor Olah, Csaba Szabo
Hydrogen sulfide (H2S) has been proposed to exert pro- as well as anti-inflammatory effects in various models of critical illness. In this study, we compared bacterial lipopolysaccharide (LPS)‑induced changes in inflammatory mediator production, indices of multiple organ injury and survival in wild‑type (WT) mice and in mice with reduced expression of one of the three H2S‑producing enzymes, cystathionine-γ-lyase (CSE), cystathionine-β-synthase (CBS) or 3-mercaptopyruvate sulfurtransferase (3MST)...
October 14, 2016: International Journal of Molecular Medicine
Siyang Yan, Amanda C Kentner
Exposure to painful procedures and/or stressors during the early neonatal period can reprogram the underlying neurocircuitry involved in nociception and neuropathic pain perception. The reprogramming of these systems can result in an enduring elevation in sensitivity towards mechanical and thermal stimuli. Recent evidence suggests that exposure to mild inflammatory mediators during the neonatal period can induce similar pain responses in both adolescent and adult rats. Therefore, we sought to profile changes in the expression of several genes across brain areas involved in the active modulation of nociception and neuropathic pain using a well-recognized model of neonatal inflammation...
October 11, 2016: Brain, Behavior, and Immunity
Anna K Stalder, Dominik Lott, Daniel S Strasser, Hans G Cruz, Andreas Krause, Peter M A Groenen, Jasper Dingemanse
AIMS: The main objectives of these two Phase 1 studies were to investigate safety and tolerability as well as the pharmacokinetic/pharmacodynamic profile of the novel potent and selective FPR2/ALX agonist ACT-389949. A challenge model was used to assess the drug's anti-inflammatory potential with the aim of selecting a dosing regimen for future patient studies. METHODS: Two double-blind, randomized Phase 1 studies investigated safety, tolerability, pharmacokinetics, and pharmacodynamics of ACT-389949 at different doses and dosing regimens...
October 11, 2016: British Journal of Clinical Pharmacology
Ana Gutiérrez-Franco, Herena Eixarch, Carme Costa, Vanessa Gil, Mireia Castillo, Laura Calvo-Barreiro, Xavier Montalban, José A Del Río, Carmen Espejo
Semaphorin 7A (sema7A) is classified as an immune semaphorin with dual functions in the immune system and in the central nervous system (CNS). These molecules are of interest due to their potential role in multiple sclerosis (MS), which is a chronic demyelinating and neurodegenerative disease of autoimmune origin. In this study, we elucidated the role of sema7A in neuroinflammation using both in vitro and in vivo experimental models. In an in vitro model of neuroinflammation, using cerebellar organotypic slice cultures, we observed that challenge with lipopolysaccharide (LPS) endotoxin did not affect demyelination or cell death in sema7A-deficient cultures compared to wild-type cultures...
October 6, 2016: Molecular Neurobiology
Xiaolan Cui, Qian Chen, Zhen Dong, Longmei Xu, Tianfei Lu, Dawei Li, Jiangjun Zhang, Ming Zhang, Qiang Xia
Sirtuin 1 (Sirt1) is a deacetylase that regulates many cellular processes in the liver, and so far its role in endotoxemic liver injury is elusive. So we conditionally inactivate Sirt1 in murine hepatocytes to determine its role in d-galactosamine (GalN)/lipopolysaccharide (LPS)-induced liver damage, which is a well-established experimental model mimicking septic liver injury and fulminant hepatitis. Ablation of Sirt1 shows remarkable protection against GalN/LPS-induced liver injury, which is a result of enhanced NF-κB response because knockdown of RelA/p65 negates the protective effect of Sirt1 knockout...
October 6, 2016: Cell Death & Disease
Jun-Yan Liu, Christophe Morisseau, Huazhang Huang, Bruce D Hammock
ETHNOPHARMACOLOGICAL RELEVANCE: Inhibition of soluble epoxide hydrolase (sEH) has been extensively reported to be anti-inflammatory in multiple animal models. Some anti-inflammatory traditional Chinese medicines (TCMs) and a few natural compounds were also found to be inhibitory to sEH in vitro. AIM OF THE STUDY: To determine whether the active intergradient (AI) against sEH of anti-inflammatory TCMs in vitro is anti-inflammatory in vivo and the sEH inhibitory action of the AI contributes to its anti-inflammatory effect in vivo...
October 1, 2016: Journal of Ethnopharmacology
Giovanna Mulas, Elena Espa, Sandro Fenu, Saturnino Spiga, Giovanni Cossu, Elisabetta Pillai, Ezio Carboni, Gabriella Simbula, Dragana Jadžić, Fabrizio Angius, Stefano Spolittu, Barbara Batetta, Daniela Lecca, Andrea Giuffrida, Anna R Carta
Neuroinflammation is associated with l-DOPA treatment in Parkinson's disease (PD), suggesting a role in l-DOPA-induced dyskinesia (LID), however it is unclear whether increased inflammation is specifically related to the dyskinetic outcome of l-DOPA treatment. Diversely from oral l-DOPA, continuous intrajejunal l-DOPA infusion is associated with very low dyskinetic outcome in PD patients. We reproduced these regimens of administration in 6-OHDA-lesioned hemiparkinsonian rats, where dyskinetic responses and striatal neuroinflammation induced by chronic pulsatile (DOPAp) or continuous (DOPAc) l-DOPA were compared...
September 30, 2016: Experimental Neurology
Lourdes Fernández de Cossío, Andrea Guzmán, Suzanne van der Veldt, Giamal N Luheshi
Environmental challenges to the maternal immune system during pregnancy have been associated with an increase in the frequency of neurodevelopmental disorders such as Autism Spectrum Disorders (ASD) appearing in the offspring. Microglia, the brain's resident immune-cells, are now known to be critically involved in normal brain development, shaping connections between neurons by pruning superfluous synaptic spines. Our aim was to investigate whether maternal infection during critical stages of gestation compromises the role of microglia in sculpting neuronal circuits...
September 30, 2016: Brain, Behavior, and Immunity
J L Leatherwood, K L Gehl, J A Coverdale, C E Arnold, R A Dabareiner, K N Walter, E D Lamprecht
Fourteen yearling Quarter horses (351 to 470 kg) were utilized in a randomized complete block design to evaluate potential of glucosamine hydrochloride (HCl) to mitigate intra-articular inflammation following a single inflammatory insult. Horses were blocked by BW, age, and sex, and randomly assigned to treatments for a 98-d experiment. Treatments consisted of a control diet (CON; = 7) fed 1% BW per d (as-fed) of concentrate only or a treatment diet ( = 7) of concentrate top dressed with 30 mg/kg BW glucosamine HCl (99...
August 2016: Journal of Animal Science
Valentina Villa, Stefano Thellung, Adriana Bajetto, Elena Gatta, Mauro Robello, Federica Novelli, Bruno Tasso, Michele Tonelli, Tullio Florio
We tested the efficacy of novel cyclooxygenase 2 (COX-2) inhibitors in counteracting glia-driven neuroinflammation induced by the amyloidogenic prion protein fragment PrP90-231 or lipopolysaccharide (LPS). In search for molecules with higher efficacy than celecoxib, we focused our study on its 2,3-diaryl-1,3-thiazolidin-4-one analogues. As experimental models, we used the immortalized microglial cell line N9, rat purified microglial primary cultures, and mixed cultures of astrocytes and microglia. Microglia activation in response to PrP90-231 or LPS was characterized by growth arrest, morphology changes and the production of reactive oxygen species (ROS)...
September 22, 2016: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
Kidong Kang, Minho Won, Jae-Min Yuk, Chan-Yong Park, Hee Sun Byun, Kyeong Ah Park, So-Ra Lee, Young-Goo Kang, Han-Ming Shen, Ill Young Lee, Gang Min Hur
A specific small-molecule inhibitor of the TLR4 signaling complex upstream of the IKK would likely provide therapeutic benefit for NF-κB-mediated inflammatory disease. We previously identified brazilin as a selective upstream IKK inhibitor targeting the Myddosome complex. In this study, using a cell-based ubiquitination assay for IRAK1 and a chemical library comprising a series of structural analogues of brazilin, a novel small molecule, 2-hydroxy-5,6-dihydroisoindolo[1,2-a]isoquinoline-3,8-dione (IinQ), was identified as a selective and potent inhibitor of IRAK1-dependent NF-κB activation upon TLR4 ligation...
September 21, 2016: Biochemical Pharmacology
Mieke Veltman, Marta Stolarczyk, Danuta Radzioch, Gabriella Wojewodka, Juan B De Sanctis, Willem A Dik, Oleh Dzyubachyk, Tamas Oravecz, Ismé De Kleer, Bob J Scholte
Progressive lung disease with early onset is the main cause of mortality and morbidity in Cystic Fibrosis patients. Here we report a reduction of Sphingosine-1-Phosphate (S1P) in the lung of unchallenged Cftrtm1EUR F508del CFTR mutant mice. This correlates with enhanced infiltration by inducible nitric oxide synthase (iNOS) expressing granulocytes, B- and T-cells. Furthermore, the ratio of macrophage derived dendritic cells (MoDC) to conventional dendritic cells (cDC) is higher in mutant mouse lung, consistent with unprovoked inflammation...
September 23, 2016: American Journal of Physiology. Lung Cellular and Molecular Physiology
Felicia Di Falco, Matteo Cammarata, Aiti Vizzini
Lysozyme is an important defense molecule of the innate immune system. Known for its bactericidal properties, lysozyme catalyzes the hydrolysis of b-(1,4)-glycosidic bonds between the N-acetyl glucosamine and N-acetyl muramic acid in the peptidoglycan layer of bacterial cell walls. In this study, the complete coding sequence of four g-type lysozymes were identified in Ciona intestinalis. Phylogenetic analysis and modelling supported the hypothesis of a close relationship with the vertebrate g-type lysozymes suggesting that the C...
September 20, 2016: Developmental and Comparative Immunology
Da Kyung Yoo, Sung-Ho Lee
Lipopolysaccharide (LPS), an endotoxin, elicits strong immune responses in mammals. Several lines of evidence demonstrate that LPS challenge profoundly affects female reproductive function. For example, LPS exposure affects steroidogenesis and folliculogenesis, resulting in delayed puberty onset. The present study was conducted to clarify the mechanism underlying the adverse effect of LPS on the delayed puberty in female rats. LPS was daily injected for 5 days (50 μg/kg, PND 25-29) to treated animals and the date at VO was evaluated through daily visual examination...
June 2016: Balsaeng'gwa Saengsig
Vahid Amini, Hossein Kazemian, Jalil Kardan Yamchi, Seifu Gizaw Feyisa, Saeed Aslani, Aref Shavalipour, Hamidreza Houri, Mohammadneshvan Hoorijani, Mehrdad Halaji, Hamid Heidari
BACKGROUND: Salmonella enterica serovar Typhimurium (S. Typhimurium) causes gastroenteritis in humans and paratyphoid disease in some animals. Given the emergence of antibiotic resistance, vaccines are more effective than chemotherapy in disease control. OBJECTIVES: The aim of this experimental study was to evaluate the immunogenicity of diphtheria toxoid (DT) conjugated with S. Typhimurium -derived OPS (O side chain isolation) in mice to determine its potential as a vaccine candidate against salmonellosis...
July 2016: Iranian Red Crescent Medical Journal
Ana S Leal, Michael B Sporn, Patricia A Pioli, Karen T Liby
Because the 5-year survival rate for pancreatic cancer remains under 10%, new drugs are needed for the prevention and treatment of this devastating disease. Patients with chronic pancreatitis have a 12-fold higher risk of developing pancreatic cancer. LSL-Kras(G12D/+);Pdx-1-Cre (KC) mice replicate the genetics, symptoms and histopathology found in human pancreatic cancer. Immune cells infiltrate into the pancreas of these mice and produce inflammatory cytokines that promote tumor growth. KC mice are particularly sensitive to the effects of lipopolysaccharide (LPS), as only 48% of KC mice survived an LPS challenge while 100% of wildtype (WT) mice survived...
September 22, 2016: Carcinogenesis
Szilamér Ferenczi, Krisztián Szegi, Zsuzsanna Winkler, Teréz Barna, Krisztina J Kovács
Inflammatory bowel disease shows increasing prevalence, however its pathomechanism and treatment is not fully resolved. Prebiotics are non-digestible carbohydrates which might provide an alternative to treat inflammatory conditions in the gut due to their positive effects either on the microbiome or through their direct effect on macrophages and mucosa. To test the protective effects of an oligomannan prebiotic, yeast cell wall mannooligosaccharide (MOS) was administered in dextran-sulphate-sodium (DSS)-induced mouse model of acute colitis...
2016: Scientific Reports
Sarah L Appleby, Claudia-Gabriela Mitrofan, Alexi Crosby, Kim Hoenderdos, Katharine Lodge, Paul D Upton, Clara M Yates, Gerard B Nash, Edwin R Chilvers, Nicholas W Morrell
Bone morphogenetic protein (BMP)9 is a circulating growth factor that is part of the TGF-β superfamily and is an essential regulator of vascular endothelial homeostasis. Previous studies have suggested a role for BMP9 signaling in leukocyte recruitment to the endothelium, but the directionality of this effect and underlying mechanisms have not been elucidated. In this study, we report that BMP9 upregulates TLR4 expression in human endothelial cells and that BMP9 pretreatment synergistically increases human neutrophil recruitment to LPS-stimulated human endothelial monolayers in an in vitro flow adhesion assay...
September 19, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
Arjun Balakrishnan, Priya DasSarma, Oindrilla Bhattacharjee, Jong Myoung Kim, Shiladitya DasSarma, Dipshikha Chakravortty
Bactericidal/permeability-increasing protein (BPI) had been shown to possess anti-inflammatory and endotoxin neutralizing activity by interacting with LPS of Gram-negative bacteria. The current study examines the feasibility of using murine BPI (mBPI) expressed on halophilic Archaeal gas vesicle nanoparticles (GVNPs) for the treatment of endotoxemia in high-risk patients, using a murine model of D-galactosamine-induced endotoxic shock. Halobacterium sp. NRC-1was used to express the N-terminal 199 amino acid residues of mBPI fused to the GVNP GvpC protein, and bound to the surface of the haloarchaeal GVNPs...
2016: Scientific Reports
Ling-Ling An, Jacob V Gorman, Geoffrey Stephens, Bonnie Swerdlow, Paul Warrener, Jessica Bonnell, Tomas Mustelin, Michael Fung, Roland Kolbeck
Severe bacterial infection results in both uncontrolled inflammation and immune suppression in septic patients. Although there is ample evidence that complement activation provokes overwhelming pro-inflammatory responses, whether or not it plays a role in immune suppression in this case is unclear. Here, we identify that complement C5a directly participates in negative regulation of immune responses to bacteria-induced inflammation in an ex vivo model of human whole blood. Challenge of whole blood with heat-killed Pseudomonas aeruginosa induces PD-L1 expression on monocytes and the production of IL-10 and TGF-β, which we show to be inhibited by C5a blockade...
2016: Scientific Reports
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