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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
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
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
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
Bruna Araujo David, Rafael Machado Rezende, Maísa Mota Antunes, Mônica Morais Santos, Maria Alice Freitas Lopes, Ariane Barros Diniz, Rafaela Vaz Sousa Pereira, Sarah Cozzer Marchesi, Débora Moreira Alvarenga, Brenda Naemi Nakagaki, Alan Moreira Araújo, Daniela Silva Dos Reis, Renata Monti Rocha, Pedro Elias Marques, Woo-Yong Lee, Justin Deniset, Pei Xiong Liew, Stephen Rubino, Laura Cox, Vanessa Pinho, Thiago Mattar Cunha, Gabriel Rocha Fernandes, André Gustavo Oliveira, Mauro Martins Teixeira, Paul Kubes, Gustavo Batista Menezes
BACKGROUND & AIMS: Resident macrophages are derived from yolk sac precursors and seed the liver during embryogenesis. Native cells may be replaced by bone marrow precursors during extensive injuries, irradiation and infections. We investigated the liver populations of myeloid immune cells and their location as well as the dynamics of phagocyte repopulation after full depletion. The effects on liver function due to the substitution of original phagocytes by bone marrow-derived surrogates were also examined...
August 25, 2016: Gastroenterology
Paaqua Grant, Tara Maga, Anna Loshakov, Rishi Singhal, Aminah Wali, Jennifer Nwankwo, Kaitlin Baron, Diana Johnson
Genes that code for proteins involved in organelle biogenesis and intracellular trafficking produce products that are critical in normal cell function . Conserved orthologs of these are present in most or all eukaryotes, including Drosophila melanogaster Some of these genes were originally identified as eye color mutants with decreases in both types of pigments found in the fly eye. These criteria were used for identification of such genes, four eye color mutations that are not annotated in the genome sequence: chocolate, maroon, mahogany, and red Malpighian tubules were molecularly mapped and their genome sequences have been evaluated...
October 13, 2016: G3: Genes—Genomes—Genetics
Zuzet Martinez Cordova, Anna Grönholm, Ville Kytölä, Valentina Taverniti, Sanna Hämäläinen, Saara Aittomäki, Wilhelmiina Niininen, Ilkka Junttila, Antti Ylipää, Matti Nykter, Marko Pesu
The proprotein convertase enzyme FURIN processes immature pro-proteins into functional end- products. FURIN is upregulated in activated immune cells and it regulates T-cell dependent peripheral tolerance and the Th1/Th2 balance. FURIN also promotes the infectivity of pathogens by activating bacterial toxins and by processing viral proteins. Here, we evaluated the role of FURIN in LysM+ myeloid cells in vivo. Mice with a conditional deletion of FURIN in their myeloid cells (LysMCre-fur(fl/fl)) were healthy and showed unchanged proportions of neutrophils and macrophages...
August 5, 2016: Oncotarget
Kana Miyata, Masahiro Hayafune, Yoshihiro Kobae, Hanae Kaku, Yoko Nishizawa, Yoshiki Masuda, Naoto Shibuya, Tomomi Nakagawa
In legume-specific rhizobial symbiosis, host plants perceive rhizobial signal molecules, Nod factors, by a couple of LysM receptor like kinases, NFR1/LYK3 and NFR5/NFP, and activate symbiotic responses through the downstream signaling components required also for arbuscular mycorrhizal (AM) symbiosis. Recently, rice NFR1/LYK3 ortholog, OsCERK1, was shown to play crucial roles for AM symbiosis. On the other hand, the roles of NFR5/NFP ortholog in rice have not been elucidated, while it has been shown that NFR5/NFP orthologs, Parasponia PaNFR5 and tomato SlRLK10, engage in AM symbiosis...
August 12, 2016: Plant & Cell Physiology
Gang Zhao, Liping Liu, Richard M Peek, Xishan Hao, D Brent Polk, Hui Li, Fang Yan
EGF receptor (EGFR) in tumor cells serves as a tumor promoter. However, information about EGFR activation in macrophages in regulating M2 polarization and tumor development is limited. This study aimed to investigate the effects of EGFR activation in macrophages on M2 polarization and development of gastrointestinal tumors. IL-4, a cytokine to elicit M2 polarization, stimulated release of an EGFR ligand, HB-EGF, and transactivation and down-regulation of EGFR in Raw 264.7 cells and peritoneal macrophages from WT mice...
September 23, 2016: Journal of Biological Chemistry
Akira Akamatsu, Ko Shimamoto, Yoji Kawano
Rice is one of the most important food crops, feeding about half population in the world. Rice pathogens cause enormous damage to rice production worldwide. In plant immunity research, considerable progress has recently been made in our understanding of the molecular mechanisms underlying microbe-associated molecular pattern (MAMP)-triggered immunity. Using genome sequencing and molecular techniques, a number of new MAMPs and their receptors have been identified in the past two decades. Notably, the mechanisms for chitin perception via the lysine motif (LysM) domain-containing receptor OsCERK1, as well as the mechanisms for bacterial MAMP (e...
August 2016: Current Genomics
Yashaswini Kannan, Jimena Perez-Lloret, Yanda Li, Lewis J Entwistle, Hania Khoury, Stamatia Papoutsopoulou, Radma Mahmood, Nuha R Mansour, Stanley Ching-Cheng Huang, Edward J Pearce, Luiz Pedro S de Carvalho, Steven C Ley, Mark S Wilson
Persistent TH2 cytokine responses following chronic helminth infections can often lead to the development of tissue pathology and fibrotic scarring. Despite a good understanding of the cellular mechanisms involved in fibrogenesis, there are very few therapeutic options available, highlighting a significant medical need and gap in our understanding of the molecular mechanisms of TH2-mediated immunopathology. In this study, we found that the Map3 kinase, TPL-2 (Map3k8; Cot) regulated TH2-mediated intestinal, hepatic and pulmonary immunopathology following Schistosoma mansoni infection or S...
August 2016: PLoS Pathogens
Yashaswini Kannan, Yanda Li, Stephanie M Coomes, Isobel S Okoye, Victoria S Pelly, Srividya Sriskantharajah, Eva Gückel, Lauren Webb, Stephanie Czieso, Nikolay Nikolov, Andrew S MacDonald, Steven C Ley, Mark S Wilson
BACKGROUND: The molecular and cellular pathways driving the pathogenesis of severe asthma are poorly defined. Tumor progression locus 2 (TPL-2) (COT, MAP3K8) kinase activates the MEK1/2-extracellular-signal regulated kinase 1/2 MAP kinase signaling pathway following Toll-like receptor, TNFR1, and IL-1R stimulation. OBJECTIVE: TPL-2 has been widely described as a critical regulator of inflammation, and we sought to investigate the role of TPL-2 in house dust mite (HDM)-mediated allergic airway inflammation...
July 5, 2016: Journal of Allergy and Clinical Immunology
Roham Parsa, Harald Lund, Ivana Tosevski, Xing-Mei Zhang, Ursula Malipiero, Jan Beckervordersandforth, Doron Merkler, Marco Prinz, Alexandra Gyllenberg, Tojo James, Andreas Warnecke, Jan Hillert, Lars Alfredsson, Ingrid Kockum, Tomas Olsson, Adriano Fontana, Tobias Suter, Robert A Harris
Intracerebral levels of Transforming Growth Factor beta (TGFβ) rise rapidly during the onset of experimental autoimmune encephalomyelitis (EAE), a mouse model of Multiple Sclerosis (MS). We addressed the role of TGFβ responsiveness in EAE by targeting the TGFβ receptor in myeloid cells, determining that Tgfbr2 was specifically targeted in monocyte-derived dendritic cells (moDCs) but not in CNS resident microglia by using bone-marrow chimeric mice. TGFβ responsiveness in moDCs was necessary for the remission phase since LysM(Cre) Tgfbr2(fl/fl) mice developed a chronic form of EAE characterized by severe demyelination and extensive infiltration of activated moDCs in the CNS...
November 2016: Glia
Min Jung Lee, So Jin Bing, Jonghee Choi, Minhee Jang, Gihyun Lee, Hyunkyoung Lee, Byung Soo Chang, Youngheun Jee, Sung Joong Lee, Ik-Hyun Cho
BACKGROUND: The inflammatory myeloid cell activation is one of the hallmarks of experimental autoimmune encephalomyelitis (EAE), yet the in vivo role of the inflammatory myeloid cell activation in EAE has not been clearly resolved. It is well-known that IKK/NF-κB is a key signaling pathway that regulates inflammatory myeloid activation. METHODS: We investigated the in vivo role of inflammatory myeloid cell activation in myelin oligodendrocyte glycoprotein (MOG) peptides-induced EAE using myeloid cell type-specific ikkβ gene conditional knockout-mice (LysM-Cre/Ikkβ (F/F) )...
2016: Molecular Neurodegeneration
Maitreyi Shivkumar, Clara Lawler, Ricardo Milho, Philip G Stevenson
UNLABELLED: Herpes simplex virus 1 (HSV-1) enters mice via olfactory epithelial cells and then colonizes the trigeminal ganglia (TG). Most TG nerve endings are subepithelial, so this colonization implies subepithelial viral spread, where myeloid cells provide an important line of defense. The outcome of infection of myeloid cells by HSV-1 in vitro depends on their differentiation state; the outcome in vivo is unknown. Epithelial HSV-1 commonly infected myeloid cells, and Cre-Lox virus marking showed nose and lung infections passing through LysM-positive (LysM(+)) and CD11c(+) cells...
October 1, 2016: Journal of Virology
S R Rasmussen, W Füchtbauer, M Novero, V Volpe, N Malkov, A Genre, P Bonfante, J Stougaard, S Radutoiu
Functional divergence of paralogs following gene duplication is one of the mechanisms leading to evolution of novel pathways and traits. Here we show that divergence of Lys11 and Nfr5 LysM receptor kinase paralogs of Lotus japonicus has affected their specificity for lipochitooligosaccharides (LCOs) decorations, while the innate capacity to recognize and induce a downstream signalling after perception of rhizobial LCOs (Nod factors) was maintained. Regardless of this conserved ability, Lys11 was found neither expressed, nor essential during nitrogen-fixing symbiosis, providing an explanation for the determinant role of Nfr5 gene during Lotus-rhizobia interaction...
2016: Scientific Reports
Kang Ho Kim, Jae Man Lee, Ying Zhou, Sanjiv Harpavat, David D Moore
Liver fibrosis is a reversible wound-healing process that is protective in the short term, but prolonged fibrotic responses lead to excessive accumulation of extracellular matrix components that suppresses hepatocyte regeneration, resulting in permanent liver damage. Upon liver damage, nonparenchymal cells including immune cells and hepatic stellate cells (HSCs) have crucial roles in the progression and regression of liver fibrosis. Here, we report differential roles of the glucocorticoid receptor (GR), acting in immune cells and HSCs, in liver fibrosis...
August 2016: Molecular Endocrinology
Minfeng Yu, Jing Yang, Minliang Guo
Lysin motif (LysM) is a highly conserved carbohydrate binding module that is widely present in proteins from both prokaryotes and eukaryotes. LysM domains from many LysM-containing proteins can be taken out of their natural context and retain their ability to bind peptidoglycan. Therefore, LysM has enormous potential for applications in both industry and medicine. This potential has stimulated an intensive search for LysM modules with different evolutionary origins. The p60 protein (Lm-p60) is an NlpC/P60-containing peptidoglycan hydrolase secreted by Listeria monocytogenes...
June 22, 2016: Bioengineered
Dennis J Wu, Ran Gu, Ritu Sarin, Regina Zavodovskaya, Chia-Pei Chen, Blaine A Christiansen, Iannis E Adamopoulos
Recently, autophagy-related proteins were shown to regulate osteoclast mediated bone resorption, a critical process in autoimmune diseases such as rheumatoid arthritis. However, the role of autophagy-linked FYVE containing protein, WDFY3, in osteoclast biology remains elusive. WDFY3 is a master regulator in selective autophagy for clearing ubiquitinated protein aggregates and has been linked with rheumatoid arthritis. Herein, we used a series of WDFY3 transgenic mice (Wdfy3(lacZ) and Wdfy3(loxP)) to investigate the function of WDFY3 in osteoclast development and function...
September 2016: Journal of Autoimmunity
David N Paglia, Xiaochuan Yang, Judith Kalinowski, Sandra Jastrzebski, Hicham Drissi, Joseph Lorenzo
Runt-related transcription factor 1 (Runx1), a master regulator of hematopoiesis, is expressed in preosteoclasts. Previously we evaluated the bone phenotype of CD11b-Cre Runx1(fl/fl) mice and demonstrated enhanced osteoclasts and decreased bone mass in males. However, an assessment of the effects of Runx1 deletion in female osteoclast precursors was impossible with this model. Moreover, the role of Runx1 in myeloid cell differentiation into other lineages is unknown. Therefore, we generated LysM-Cre Runx1(fl/fl) mice, which delete Runx1 equally (∼80% deletion) in myeloid precursor cells from both sexes and examined the capacity of these cells to differentiate into osteoclasts and phagocytic and antigen-presenting cells...
August 2016: Endocrinology
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