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https://www.readbyqxmd.com/read/28190384/lactic-acid-bacteria-with-concomitant-il-17-il-23-and-tnf%C3%AE-binding-ability-for-the-treatment-of-inflammatory-bowel-disease
#1
Staša Kosler, Borut Štrukelj, Aleš Berlec
BACKGROUND: Neutralization of proinflammatory cytokines is an established strategy in the treatment of inflammatory bowel disease (IBD). Systemic anti-TNFα antibodies have been used in the clinics for several years, while anti-IL-17/IL-23 antibodies have been less successful so far. We report the development of safe lactic acid bacterium Lb. salivarius with the ability to simultaneously bind IL-17A, IL-23 and TNFα that could be administered orally for the treatment of IBD. METHODS: Three different cytokine-binding non-Ig scaffolds (anti-IL-17A fynomer, anti-IL-23-binding adnectin and anti-TNFα-binding affibody) were cloned and expressed in L...
10, 2017: Current Pharmaceutical Biotechnology
https://www.readbyqxmd.com/read/28165624/myeloid-myd88-contributes-to-ethanol-induced-liver-injury-in-mice-linking-hepatocellular-death-to-inflammation
#2
Hao Zhou, Minja Yu, Sanjoy Roychowdhury, Carlos Sanz-Garcia, Katherine A Pollard, Megan R McMullen, Xiuli Liu, Xiaoxia Li, Laura E Nagy
BACKGROUND: Toll-like receptor 4 (TLR4) is critical for ethanol-induced liver injury. TLR4 signaling is mediated by two proximal adaptor molecules: myeloid differentiation primary-response protein (MyD88) and TLR-domain-containing adapter-inducing interferon-β (TRIF). Studies utilizing global knock-outs of MyD88 and TRIF identified a predominant role for TRIF signaling in the progression of ethanol-induced liver injury. In contrast, IL1 receptor, which signals solely via the MyD88 pathway, is also known to mediate ethanol-induced liver injury...
February 6, 2017: Alcoholism, Clinical and Experimental Research
https://www.readbyqxmd.com/read/28120642/a-novel-mouse-model-of-conditional-irak-m-deficiency-in-myeloid-cells-application-in-lung-pseudomonas-aeruginosa-infection
#3
Di Jiang, Jennifer Matsuda, Reena Berman, Niccolette Schaefer, Connor Stevenson, James Gross, Bicheng Zhang, Amelia Sanchez, Liwu Li, Hong Wei Chu
Myeloid cells such as macrophages are critical to innate defense against infection. IL-1 receptor-associated kinase M (IRAK-M) is a negative regulator of TLR signaling during bacterial infection, but the role of myeloid cell IRAK-M in bacterial infection is unclear. Our goal was to generate a novel conditional knockout mouse model to define the role of myeloid cell IRAK-M during bacterial infection. Myeloid cell-specific IRAK-M knockout mice were generated by crossing IRAK-M floxed mice with LysM-Cre knock-in mice...
February 2017: Innate Immunity
https://www.readbyqxmd.com/read/28120013/secretory-expression-and-surface-display-of-a-new-and-biologically-active-single-chain-insulin-sci-59-analog-by-lactic-acid-bacteria
#4
Ruifeng Mao, Dongli Wu, Shimeng Hu, Kangping Zhou, Man Wang, Yefu Wang
Insulin plays an important role in drug therapies for diabetes mellitus and as the main route of insulin delivery, subcutaneous injection may cause local discomfort, hypoglycemia, hyperinsulinemia, and patient non-compliance. Therefore, oral delivery of insulin is more preferred. However, there is a low bioavailability due to insulin degradation by proteolytic enzymes and severe pH conditions along the gastrointestinal tract. In order to use the food-grade bacteria lactic acid bacteria (LAB) as oral delivery vehicles, a new and bioactive single-chain insulin (SCI-59) analog, containing the insulin B- and A-chains connected by an eight-residue linker (RSRGLPFR), was secretory expressed in Lactococcus lactis NZ3900 without using an antibiotic resistance gene and displayed onto the surface of various non-viable bacteria (NVBs) without genetic modification...
January 24, 2017: Applied Microbiology and Biotechnology
https://www.readbyqxmd.com/read/28099857/a-systems-approach-reveals-mavs-signaling-in-myeloid-cells-as-critical-for-resistance-to-ebola-virus-in-murine-models-of-infection
#5
Mukta Dutta, Shelly J Robertson, Atsushi Okumura, Dana P Scott, Jean Chang, Jeffrey M Weiss, Gail L Sturdevant, Friederike Feldmann, Elaine Haddock, Abhilash I Chiramel, Sanket S Ponia, Jonathan D Dougherty, Michael G Katze, Angela L Rasmussen, Sonja M Best
The unprecedented 2013-2016 outbreak of Ebola virus (EBOV) resulted in over 11,300 human deaths. Host resistance to RNA viruses requires RIG-I-like receptor (RLR) signaling through the adaptor protein, mitochondrial antiviral signaling protein (MAVS), but the role of RLR-MAVS in orchestrating anti-EBOV responses in vivo is not known. Here we apply a systems approach to MAVS(-/-) mice infected with either wild-type or mouse-adapted EBOV. MAVS controlled EBOV replication through the expression of IFNα, regulation of inflammatory responses in the spleen, and prevention of cell death in the liver, with macrophages implicated as a major cell type influencing host resistance...
January 17, 2017: Cell Reports
https://www.readbyqxmd.com/read/28062700/intravital-imaging-of-neutrophil-recruitment-reveals-the-efficacy-of-fpr1-blockade-in-hepatic-ischemia-reperfusion-injury
#6
Masaki Honda, Takayuki Takeichi, Shintaro Hashimoto, Daiki Yoshii, Kaori Isono, Shintaro Hayashida, Yuki Ohya, Hidekazu Yamamoto, Yasuhiko Sugawara, Yukihiro Inomata
Neutrophils are considered responsible for the pathophysiological changes resulting from hepatic ischemia-reperfusion (I/R) injury, which is a complication of trauma, shock, liver resection, and transplantation. Recently, evidence is accumulating that formyl-peptide receptor (FPR) signaling constitutes an important danger signal that guides neutrophils to sites of inflammation. This study aimed to investigate dynamic neutrophil recruitment using two-photon laser-scanning microscopy (TPLSM) in response to FPR1 blockade during hepatic I/R...
January 6, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28003382/mek1-2-inhibition-promotes-macrophage-reparative-properties
#7
Matthew E Long, William E Eddy, Ke-Qin Gong, Lara L Lovelace-Macon, Ryan S McMahan, Jean Charron, W Conrad Liles, Anne M Manicone
Macrophages have important functional roles in regulating the timely promotion and resolution of inflammation. Although many of the intracellular signaling pathways involved in the proinflammatory responses of macrophages are well characterized, the components that regulate macrophage reparative properties are less well understood. We identified the MEK1/2 pathway as a key regulator of macrophage reparative properties. Pharmacological inhibition of the MEK1/2 pathway by a MEK1/2 inhibitor (MEKi) significantly increased expression of IL-4/IL-13 (M2)-responsive genes in murine bone marrow-derived and alveolar macrophages...
January 15, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/27990146/comparative-transcriptomic-analysis-of-virulence-factors-in-leptosphaeria-maculans-during-compatible-and-incompatible-interactions-with-canola
#8
Humira Sonah, Xuehua Zhang, Rupesh K Deshmukh, M Hossein Borhan, W G Dilantha Fernando, Richard R Bélanger
Leptosphaeria maculans is a hemibiotrophic fungus that causes blackleg of canola (Brassica napus), one of the most devastating diseases of this crop. In the present study, transcriptome profiling of L. maculans was performed in an effort to understand and define the pathogenicity genes that govern both the biotrophic and the necrotrophic phase of the fungus, as well as those that separate a compatible from an incompatible interaction. For this purpose, comparative RNA-seq analyses were performed on L. maculans isolate D5 at four different time points following inoculation on susceptible cultivar Topas-DH16516 or resistant introgression line Topas-Rlm2...
2016: Frontiers in Plant Science
https://www.readbyqxmd.com/read/27927724/myeloid-bmal1-deletion-increases-monocyte-recruitment-and-worsens-atherosclerosis
#9
Mingyu Huo, Yuhong Huang, Dan Qu, Hongsong Zhang, Wing Tak Wong, Ajay Chawla, Yu Huang, Xiao Yu Tian
BMAL1, the nonredundant transcription factor in the core molecular clock, has been implicated in cardiometabolic diseases in mice and humans. BMAL1 controls the cyclic trafficking of Ly6c(hi) monocytes to sites of acute inflammation. Myeloid deficiency of Bmal1 also worsens chronic inflammation in diet-induced obesity. We studied whether myeloid Bmal1 deletion promotes atherosclerosis by enhancing monocyte recruitment to atherosclerotic lesion. By generating Bmal1(FloxP/FloxP);LysM(Cre) mice on the Apoe(-/-) background, we showed that Bmal1 deletion in myeloid cells increased the size of atherosclerotic lesion...
December 7, 2016: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/27911046/verticillium-dahliae-lysm-effectors-differentially-contribute-to-virulence-on-plant-hosts
#10
Anja Kombrink, Hanna Rovenich, Xiaoqian Shi-Kunne, Eduardo Rojas-Padilla, Grardy C M van den Berg, Emmanouil Domazakis, Ronnie de Jonge, Dirk-Jan Valkenburg, Andrea Sánchez-Vallet, Michael F Seidl, Bart P H J Thomma
Chitin-binding LysM effectors contribute to virulence of various plant pathogenic fungi that are causal agents of foliar diseases. Here, we report on LysM effectors of the soil-borne fungal vascular wilt pathogen Verticillium dahliae. Comparative genomics revealed three core LysM effectors that are conserved in a collection of V. dahliae strains. Remarkably, and in contrast to the previously studied LysM effectors of other plant pathogens, no expression of core LysM effectors was monitored in planta in a taxonomically diverse panel of host plants...
December 2, 2016: Molecular Plant Pathology
https://www.readbyqxmd.com/read/27906172/inflammatory-macrophages-can-transdifferentiate-into-myofibroblasts-during-renal-fibrosis
#11
Xiao-Ming Meng, Shuang Wang, Xiao-Ru Huang, Chen Yang, Jun Xiao, Yang Zhang, Ka-Fai To, David J Nikolic-Paterson, Hui-Yao Lan
Myofibroblasts play a central role in renal fibrosis although the origin of these cells remains controversial. We recently reported that bone marrow-derived macrophages can give rise to myofibroblasts through macrophage to myofibroblast transition (MMT). However, several important issues remain to be addressed, including whether MMT occurs in human kidney disease and verification of the MMT process through lineage tracing. Biopsies from a cohort of 58 patients with various forms of kidney disease were examined for MMT cells that co-express macrophage (CD68) and myofibroblast (α-smooth muscle actin, α-SMA) markers...
December 1, 2016: Cell Death & Disease
https://www.readbyqxmd.com/read/27890013/in-silico-characterization-of-a-hypothetical-protein-rv1288-of-mycobacterium-tuberculosis-containing-an-esterase-signature-and-an-uncommon-lyte-domain
#12
Arbind Kumar, Pratibha Maan, Gurpreet Singh, Jagdeep Kaur
BACKGROUND: Death toll due to tuberculosis is still rising day by day. Whole genome sequence of Mycobacterium tuberculosis has provided a platform to conduct research in order to identify the probable drug target. OBJECTIVES: Out of 4000 gene products of M. tuberculosis, approximately 40% of proteins are annotated as hypothetical. Identifying and characterizing these proteins could provide a new prescriptive for developing new TB drugs. Rv1288, a protein of M. tuberculosis H37Rv has been annotated as a hypothetical protein in database...
November 24, 2016: Current Computer-aided Drug Design
https://www.readbyqxmd.com/read/27815382/therapeutic-treatment-with-sphingosine-1-phosphate-receptor-1-ligands-reduces-pertussis-inflammatory-pathology-by-a-pertussis-toxin-insensitive-mechanism
#13
Ciaran Skerry, Karen Scanlon, Jeremy Ardanuy, Drew Roberts, Li Zhang, Hugh Rosen, Nicholas H Carbonetti
Recent data have demonstrated the potential of sphingosine-1-phosphate receptor (S1PR) agonism in the treatment of infectious diseases. Previously we used a murine model of Bordetella pertussis infection to demonstrate that treatment with the S1PR agonist AAL-R reduces pulmonary inflammation during infection. Here we show that this effect is mediated via the S1PR1 receptor on LysM+ (myeloid) cells. Signaling via this receptor results in reduced lung inflammation and cellular recruitment as well as reduced morbidity and mortality in a neonatal mouse model of disease...
November 3, 2016: Journal of Infectious Diseases
https://www.readbyqxmd.com/read/27807643/chitin-oligosaccharide-binding-to-the-lysin-motif-of-a-novel-type-of-chitinase-from-the-multicellular-green-alga-volvox-carteri
#14
Yoshihito Kitaoku, Tamo Fukamizo, Tomoyuki Numata, Takayuki Ohnuma
The chitinase-mediated defense system in higher plants has been intensively studied from physiological and structural viewpoints. However, the defense system in the most primitive plant species, such as green algae, has not yet been elucidated in details. In this study, we solved the crystal structure of a family CBM-50 LysM module attached to the N-terminus of chitinase from Volvox carteri, and successfully analyzed its chitin-binding ability by NMR spectroscopy and isothermal titration calorimetry. Trp96 of the LysM module appeared to make a CH-π stacking interaction with the reducing end sugar residue of the ligand...
January 2017: Plant Molecular Biology
https://www.readbyqxmd.com/read/27806688/rgaugury-a-pipeline-for-genome-wide-prediction-of-resistance-gene-analogs-rgas-in-plants
#15
Pingchuan Li, Xiande Quan, Gaofeng Jia, Jin Xiao, Sylvie Cloutier, Frank M You
BACKGROUND: Resistance gene analogs (RGAs), such as NBS-encoding proteins, receptor-like protein kinases (RLKs) and receptor-like proteins (RLPs), are potential R-genes that contain specific conserved domains and motifs. Thus, RGAs can be predicted based on their conserved structural features using bioinformatics tools. Computer programs have been developed for the identification of individual domains and motifs from the protein sequences of RGAs but none offer a systematic assessment of the different types of RGAs...
November 2, 2016: BMC Genomics
https://www.readbyqxmd.com/read/27770461/depletion-of-myeloid-cells-exacerbates-hepatitis-and-induces-an-aberrant-increase-in-histone-h3-in-mouse-serum
#16
Xuehua Piao, Soh Yamazaki, Sachiko Komazawa-Sakon, Sanae Miyake, Osamu Nakabayashi, Takeyuki Kurosawa, Tetsuo Mikami, Minoru Tanaka, Nico Van Rooijen, Masaki Ohmuraya, Akira Oikawa, Yuko Kojima, Soichiro Kakuta, Yasuo Uchiyama, Masato Tanaka, Hiroyasu Nakano
: Tissue-resident macrophages and bone marrow (BM)-derived monocytes play a crucial role in the maintenance of tissue homeostasis; however, their contribution to recovery from acute tissue injury is not fully understood. To address this issue, we generated an acute murine liver injury model using hepatocyte-specific Cflar-deficient (Cflar(Hep-low) ) mice. Cellular FLICE-inhibitory protein expression was down-regulated in Cflar-deficient hepatocytes, which thereby increased susceptibility of hepatocytes to death receptor-induced apoptosis...
January 2017: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/27714847/the-effects-of-aging-and-sex-steroid-deficiency-on-the-murine-skeleton-are-independent-and-mechanistically-distinct
#17
Serra Ucer, Srividhya Iyer, Ha-Neui Kim, Li Han, Christine Rutlen, Kelly Allison, Jeff D Thostenson, Rafael de Cabo, Robert L Jilka, Charles O'Brien, Maria Almeida, Stavros C Manolagas
Old age and sex steroid deficiency are the two most critical factors for the development of osteoporosis. It remains unknown, however, whether the molecular culprits of the two conditions are similar or distinct. We show herein that at 19.5 months of age-a time by which the age-dependent decline of cortical and cancellous bone mass and cortical porosity were fully manifested in C57BL/6J mice-these animals remained functionally estrogen sufficient. Transgenic mice with conditional expression of mitochondria-targeted catalase-a potent H2 O2 inactivating enzyme-in cells of the myeloid lineage (mitoCAT;LysM-Cre mice) were protected from the loss of cortical, but not cancellous, bone caused by gonadectomy in either sex...
October 7, 2016: Journal of Bone and Mineral Research: the Official Journal of the American Society for Bone and Mineral Research
https://www.readbyqxmd.com/read/27698010/circulating-soluble-il-6r-but-not-adam17-activation-drives-mononuclear-cell-migration-in-tissue-inflammation
#18
Neele Schumacher, Stefanie Schmidt, Jeanette Schwarz, Dana Dohr, Juliane Lokau, Jürgen Scheller, Christoph Garbers, Athena Chalaris, Stefan Rose-John, Björn Rabe
Neutrophil and mononuclear cell infiltration during inflammatory processes is highly regulated. The first cells at the site of infection or inflammation are neutrophils, followed by mononuclear cells. IL-6 plays an important role during inflammatory states. It has been shown in several models that the soluble form of IL-6R (sIL-6R) is involved in the recruitment of mononuclear cells by a mechanism called IL-6 trans-signaling. It had been speculated that sIL-6R was generated at the site of inflammation by shedding from neutrophils via activation of the metalloprotease ADAM17...
October 3, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/27670406/the-role-of-atrial-natriuretic-peptide-to-attenuate-inflammation-in-a-mouse-skin-wound-and-individually-perfused-rat-mesenteric-microvessels
#19
Fitz-Roy E Curry, Joyce F Clark, Yanyan Jiang, Min-Ho Kim, Roger H Adamson, Scott I Simon
We tested the hypothesis that the anti-inflammatory actions of atrial natriuretic peptide (ANP) result from the modulation of leukocyte adhesion to inflamed endothelium and not solely ANP ligation of endothelial receptors to stabilize endothelial barrier function. We measured vascular permeability to albumin and accumulation of fluorescent neutrophils in a full-thickness skin wound on the flank of LysM-EGFP mice 24 h after formation. Vascular permeability in individually perfused rat mesenteric microvessels was also measured after leukocytes were washed out of the vessel lumen...
September 2016: Physiological Reports
https://www.readbyqxmd.com/read/27594529/autophagy-deficiency-in-macrophages-enhances-nlrp3-inflammasome-activity-and-chronic-lung-disease-following-silica-exposure
#20
Forrest Jessop, Raymond F Hamilton, Joseph F Rhoderick, Pamela K Shaw, Andrij Holian
Autophagy is an important metabolic mechanism that can promote cellular survival following injury. The specific contribution of autophagy to silica-induced inflammation and disease is not known. The objective of these studies was to determine the effects of silica exposure on the autophagic pathway in macrophages, as well as the general contribution of autophagy in macrophages to inflammation and disease. Silica exposure enhanced autophagic activity in vitro in Bone Marrow derived Macrophages and in vivo in Alveolar Macrophages isolated from silica-exposed mice...
October 15, 2016: Toxicology and Applied Pharmacology
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