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https://www.readbyqxmd.com/read/29720262/upper-zone-of-growth-plate-and-cartilage-matrix-associated-protein-protects-cartilage-during-inflammatory-arthritis
#1
Fritz Seuffert, Daniela Weidner, Wolfgang Baum, Georg Schett, Michael Stock
BACKGROUND: ADAMTS aggrecanases play a major role in cartilage degeneration during degenerative and inflammatory arthritis. The cartilage-specific secreted protein Upper zone of growth plate and cartilage matrix associated protein (Ucma) has been shown to block ADAMTS-triggered aggrecanolysis in experimental osteoarthritis. Here we aimed to investigate whether and how Ucma may affect cartilage destruction and osteophyte formation in the context of inflammatory arthritis. METHODS: Ucma-ADAMTS5 protein interactions were studied using slot blot and solid phase binding assays...
May 2, 2018: Arthritis Research & Therapy
https://www.readbyqxmd.com/read/29616043/lineage-specific-analysis-of-syk-function-in-autoantibody-induced-arthritis
#2
Tamás Németh, Krisztina Futosi, Kata Szilveszter, Olivér Vilinovszki, Levente Kiss-Pápai, Attila Mócsai
Autoantibody production and autoantibody-mediated inflammation are hallmarks of a number of autoimmune diseases. The K/BxN serum-transfer arthritis is one of the most widely used models of the effector phase of autoantibody-induced pathology. Several hematopoietic lineages including neutrophils, platelets, and mast cells have been proposed to contribute to inflammation and tissue damage in this model. We have previously shown that the Syk tyrosine kinase is critically involved in the development in K/BxN serum-transfer arthritis and bone marrow chimeric experiments indicated that Syk is likely involved in one or more hematopoietic lineages during the disease course...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29602515/the-critical-role-of-c5a-as-an-initiator-of-neutrophil-mediated-autoimmune-inflammation-of-the-joint-and-skin
#3
REVIEW
Christian D Sadik, Yoshishige Miyabe, Tanya Sezin, Andrew D Luster
The deposition of IgG autoantibodies in peripheral tissues and the subsequent activation of the complement system, which leads to the accumulation of the anaphylatoxin C5a in these tissues, is a common hallmark of diverse autoimmune diseases, including rheumatoid arthritis (RA) and pemphigoid diseases (PDs). C5a is a potent chemoattractant for granulocytes and mice deficient in its precursor C5 or its receptor C5aR1 are resistant to granulocyte recruitment and, consequently, to tissue inflammation in several models of autoimmune diseases...
March 27, 2018: Seminars in Immunology
https://www.readbyqxmd.com/read/29599513/akkermansia-muciniphila-is-permissive-to-arthritis-in-the-k-bxn-mouse-model-of-arthritis
#4
Matthew L Stoll, M Kathy Pierce, Jordan A Watkins, Mingce Zhang, Pamela F Weiss, Jennifer E Weiss, Charles O Elson, Randy Q Cron, Ranjit Kumar, Casey D Morrow, Trenton R Schoeb
Studies have identified abnormalities in the microbiota of patients with arthritis. To evaluate the pathogenicity of human microbiota, we performed fecal microbial transplantation from children with spondyloarthritis and controls to germ-free KRN/B6xNOD mice. Ankle swelling was equivalent in those that received patient vs. control microbiota. Principal coordinates analysis revealed incomplete uptake of the human microbiota with over-representation of two genera (Bacteroides and Akkermansia) among the transplanted mice...
March 24, 2018: Genes and Immunity
https://www.readbyqxmd.com/read/29449195/neutrophil-microvesicles-from-healthy-control-and-rheumatoid-arthritis-patients-prevent-the-inflammatory-activation-of-macrophages
#5
Hefin I Rhys, Francesco Dell'Accio, Costantino Pitzalis, Adrian Moore, Lucy V Norling, Mauro Perretti
Microvesicles (MVs) are emerging as a novel means to enact cell-to-cell communication in inflammation. Here, we aimed to ascertain the ability of neutrophil-derived MVs to modulate target cell behaviour, the focus being the macrophage. MVs were generated in response to tumour necrosis factor-α, from healthy control neutrophils or those from rheumatoid arthritis patients. MVs were used to stimulate human monocyte-derived macrophages in vitro, or administered intra-articularly in the K/BxN mouse model of arthritis...
March 2018: EBioMedicine
https://www.readbyqxmd.com/read/29386227/role-of-11%C3%AE-hsd-type-1-in-abnormal-hpa-axis-activity-during-immune-mediated-arthritis
#6
Janko Sattler, Jinwen Tu, Shihani Stoner, Jingbao Li, Frank Buttgereit, Markus J Seibel, Hong Zhou, Mark S Cooper
Patients with chronic immune-mediated arthritis exhibit abnormal hypothalamo-pituitary-adrenal (HPA) axis activity. The basis for this abnormality is not known. Immune-mediated arthritis is associated with increased extra-adrenal synthesis of active glucocorticoids by the 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) enzyme. 11β-HSD1 is expressed in the central nervous system, including regions involved in HPA axis regulation. We examined whether altered 11β-HSD1 expression within these regions contributes to HPA axis dysregulation during arthritis...
February 2018: Endocrine Connections
https://www.readbyqxmd.com/read/29197380/a-time-course-microarray-data-analysis-reveals-consistent-dysregulated-genes-and-upstream-micrornas-in-autoantibody-mediated-arthritis
#7
Xinwen Wang, Jie Bai, Zhen Jia, Yangjun Zhu, Jijun Liu, Kun Zhang, Dingjun Hao, Lisong Heng
BACKGROUND: The purpose of this study is to identify key genes and microRNAs (miRNAs) involved in autoantibody-mediated arthritis (AMA). METHODS: A time-course microarray data (ID: GSE27492) of peripheral blood leukocytes, ankle tissue, and synovial fluid from K/BxN mouse serum-transferred mice were downloaded from Gene Expression Omnibus. Those samples were collected at days 0, 1, 3, 7, 12, and 18 after serum injection. Limma of R was employed to identify differentially expressed genes (DEGs) in samples collected at days 1-18 compared with those collected at day 0...
December 2, 2017: Journal of Orthopaedic Surgery and Research
https://www.readbyqxmd.com/read/29164814/detection-of-subclinical-arthritis-in-mice-by-a-thrombin-receptor-derived-imaging-agent
#8
Beth Friedman, Michael A Whitney, Elamprakash N Savariar, Christa Caneda, Paul Steinbach, Qing Xiong, Dina V Hingorani, Jessica Crisp, Stephen R Adams, Michael Kenner, Csilla N Lippert, Quyen T Nguyen, Monica Guma, Roger Y Tsien, Maripat Corr
OBJECTIVE: Functional imaging of synovitis could improve both early detection of rheumatoid arthritis (RA) and long-term outcomes. Given the intersection of inflammation with coagulation protease activation, this study was undertaken to examine coagulation protease activities in arthritic mice with a dual-fluorescence ratiometric activatable cell-penetrating peptide (RACPP) that has a linker, norleucine (Nle)-TPRSFL, with a cleavage site for thrombin. METHODS: K/BxN-transgenic mice with chronic arthritis and mice with day 1 passive serum-transfer arthritis were imaged in vivo for Cy5:Cy7 emission ratiometric fluorescence from proteolytic cleavage and activation of RACPPNleTPRSFL ...
January 2018: Arthritis & Rheumatology
https://www.readbyqxmd.com/read/28978351/the-caspase-8-ripk3-signaling-axis-in-antigen-presenting-cells-controls-the-inflammatory-arthritic-response
#9
Salina Dominguez, Anna B Montgomery, G Kenneth Haines, Christina L Bloomfield, Carla M Cuda
BACKGROUND: Caspase-8 is a well-established initiator of apoptosis and suppressor of necroptosis, but maintains functions beyond cell death that involve suppression of receptor-interacting serine-threonine kinases (RIPKs). A genome-wide association study meta-analysis revealed an SNP associated with risk of rheumatoid arthritis (RA) development within the locus containing the gene encoding for caspase-8. Innate immune cells, like macrophages and dendritic cells, are gaining momentum as facilitators of autoimmune disease pathogenesis, and, in particular, RA...
October 4, 2017: Arthritis Research & Therapy
https://www.readbyqxmd.com/read/28955486/nardilysin-is-involved-in-autoimmune-arthritis-via-the-regulation-of-tumour-necrosis-factor-alpha-secretion
#10
Takayuki Fujii, Eiichiro Nishi, Hiromu Ito, Hiroyuki Yoshitomi, Moritoshi Furu, Namiko Okabe, Mikiko Ohno, Kiyoto Nishi, Yusuke Morita, Yugo Morita, Masayuki Azukizawa, Akinori Okahata, Takuya Tomizawa, Takeshi Kimura, Shuichi Matsuda
OBJECTIVE: Tumour necrosis factor alpha (TNF-α) plays an important role in rheumatoid arthritis (RA). TNF-α is synthesised as a membrane-anchored precursor and is fully activated by a disintegrin and metalloproteinase 17 (ADAM17)-mediated ectodomain shedding. Nardilysin (NRDC) facilitates ectodomain shedding via activation of ADAM17. This study was undertaken to elucidate the role of NRDC in RA. METHODS: NRDC-deficient (Nrdc(-/-) ) mice and macrophage-specific NRDC-deficient (Nrdc(delM) ) mice were examined in murine RA models, collagen antibody-induced arthritis (CAIA) and K/BxN serum transfer arthritis (K/BxN STA)...
2017: RMD Open
https://www.readbyqxmd.com/read/28928247/endogenous-glucocorticoid-signaling-in-chondrocytes-attenuates-joint-inflammation-and-damage
#11
Jinwen Tu, Shihani Stoner, Phillip D Fromm, Tingyu Wang, Di Chen, Jan Tuckermann, Mark S Cooper, Markus J Seibel, Hong Zhou
Previous studies demonstrated that endogenous glucocorticoid signaling in osteoblasts promotes inflammation in murine immune arthritis. The current study determined whether disruption of endogenous glucocorticoid signaling in chondrocytes also modulates the course and severity of arthritis. Tamoxifen-inducible chondrocyte-targeted glucocorticoid receptor-knockout (chGRKO) mice were generated by breeding GRflox/flox mice with tamoxifen-inducible collagen 2a1 Cre (Col2a1-CreERT2 ) mice. Antigen-induced arthritis (AIA) and K/BxN serum transfer-induced arthritis (STIA) were induced in both chGRKO mice and their Cre-negative GRflox/flox littermates [wild type (WT)]...
January 2018: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28882929/rhob-blockade-selectively-inhibits-autoantibody-production-in-autoimmune-models-of-rheumatoid-arthritis-and-lupus
#12
Laura Mandik-Nayak, James B DuHadaway, Jennifer Mulgrew, Elizabeth Pigott, Kaylend Manley, Summer Sedano, George C Prendergast, Lisa D Laury-Kleintop
During the development of autoimmune disease, a switch occurs in the antibody repertoire of B cells so that the production of pathogenic rather than non-pathogenic autoantibodies is enabled. However, there is limited knowledge concerning how this pivotal step occurs. Here, we present genetic and pharmacological evidence of a positive modifier function for the vesicular small GTPase RhoB in specifically mediating the generation of pathogenic autoantibodies and disease progression in the K/BxN preclinical mouse model of inflammatory arthritis...
November 1, 2017: Disease Models & Mechanisms
https://www.readbyqxmd.com/read/28819701/suppressive-effects-of-tsahc-in-an-experimental-mouse-model-and-fibroblast-like-synoviocytes-of-rheumatoid-arthritis
#13
Min-Gyu Jeon, Yun-Hong Cheon, Hye-Song Lim, Sang Mi Yi, Young Sun Suh, Hyun-Ok Kim, Young-Sool Hah, Ki-Hun Park, Hae Sook Noh, Sang-Il Lee
The purpose of this study is to investigate the effect of TSAHC [4'-(p-toluenesulfonylamido)-4-hydroxychalcone] in K/BxN serum transfer arthritis model and fibroblast-like synoviocytes of rheumatoid arthritis (RA-FLS). In in vivo experiments, TSAHC attenuated the incidence and severity of arthritis in comparison with the vehicle group. Histological findings showed that TSAHC decreased the inflammation, bone erosion, cartilage damage, and osteoclasts activity in the ankle. Furthermore, we confirmed by biochemical analysis that the observations were associated with the decreased expression of proinflammatory cytokines, matrix metalloproteinases (MMPs), and RANKL in serum and ankle...
December 2017: Inflammation
https://www.readbyqxmd.com/read/28810929/the-impact-of-age-and-gut-microbiota-on-th17-and-tfh-cells-in-k-bxn-autoimmune-arthritis
#14
Fei Teng, Krysta M Felix, C Pierce Bradley, Debdut Naskar, Heqing Ma, Walid A Raslan, Hsin-Jung Joyce Wu
BACKGROUND: Age is an important risk factor for rheumatoid arthritis (RA), which often develops in middle age. However, how age-associated changes in immunity impact RA is poorly understood. Gut microbiota are known to be involved in the pathogenesis of RA, but the effects of microbiota in older subjects remain mostly unknown. METHODS: We used segmented filamentous bacteria (SFB), a gut commensal species with immunomodulatory effects, and K/BxN mice, a T cell receptor (TCR) transgenic model, to study the effect of age and microbiota on autoimmune arthritis...
August 15, 2017: Arthritis Research & Therapy
https://www.readbyqxmd.com/read/28808141/a-critical-role-for-plasma-kallikrein-in-the-pathogenesis-of-autoantibody-induced-arthritis
#15
Aizhen Yang, Junsong Zhou, Bo Wang, Jihong Dai, Robert W Colman, Wenchao Song, Yi Wu
The plasma kallikrein-kinin system (KKS) consists of serine proteases, prekallikrein (pKal) and factor XII (FXII), and a cofactor, high-MW kininogen (HK). Upon activation, activated pKal and FXII cleave HK to release bradykinin. Activation of this system has been noted in patients with rheumatoid arthritis, and its pathogenic role has been characterized in animal arthritic models. In this study, we generated 2 knockout mouse strains that lacked pKal and HK and determined the role of KKS in autoantibody-induced arthritis...
December 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28807995/regulation-of-the-cell-cycle-and-inflammatory-arthritis-by-the-transcription-cofactor-lbh-gene
#16
Shinji Matsuda, Deepa Hammaker, Katharyn Topolewski, Karoline J Briegel, David L Boyle, Steven Dowdy, Wei Wang, Gary S Firestein
Rheumatoid arthritis (RA) fibroblast-like synoviocytes (FLS) display unique aggressive behavior, invading the articular cartilage and promoting inflammation. Using an integrative analysis of RA risk alleles, the transcriptome and methylome in RA FLS, we recently identified the limb bud and heart development ( LBH ) gene as a key dysregulated gene in RA and other autoimmune diseases. Although some evidence suggests that LBH could modulate the cell cycle, the precise mechanism is unknown and its impact on inflammation in vivo has not been defined...
October 1, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28777892/therapeutic-modulation-of-plasmacytoid-dendritic-cells-in-experimental-arthritis
#17
Ramzi Nehmar, Ghada Alsaleh, Benjamin Voisin, Vincent Flacher, Alexandre Mariotte, Victoria Saferding, Antonia Puchner, Birgit Niederreiter, Thierry Vandamme, Gernot Schabbauer, Philippe Kastner, Susan Chan, Peggy Kirstetter, Martin Holcmann, Christopher Mueller, Jean Sibilia, Seiamak Bahram, Stephan Blüml, Philippe Georgel
OBJECTIVE: The role of plasmacytoid dendritic cells (PDCs) and type I interferons (IFNs) in rheumatoid arthritis (RA) remains a subject of controversy. This study was undertaken to explore the contribution of PDCs and type I IFNs to RA pathogenesis using various animal models of PDC depletion and to monitor the effect of localized PDC recruitment and activation on joint inflammation and bone damage. METHODS: Mice with K/BxN serum-induced arthritis, collagen-induced arthritis, and human tumor necrosis factor transgene insertion were studied...
November 2017: Arthritis & Rheumatology
https://www.readbyqxmd.com/read/28724439/genetic-deficiency-of-wnt5a-diminishes-disease-severity-in-a-murine-model-of-rheumatoid-arthritis
#18
Susan MacLauchlan, Maria A Zuriaga, José J Fuster, Carla M Cuda, Jennifer Jonason, Fernanda Behzadi, Jennifer Parker Duffen, G Kenneth Haines, Tamar Aprahamian, Harris Perlman, Kenneth Walsh
BACKGROUND: Rheumatoid arthritis (RA) is a common autoimmune disease characterized by chronic inflammation of the joints, leading to bone erosion and joint dysfunction. Despite the recent successes of disease-modifying anti-rheumatic drugs (DMARDs), there is still clinical need for understanding the development and molecular etiology of RA. Wnts are developmental morphogens whose roles in adult pathology are poorly characterized. Wnt5a is a member of the non-canonical family of Wnts that modulates a wide range of cell processes, including differentiation, migration, and inflammation...
July 19, 2017: Arthritis Research & Therapy
https://www.readbyqxmd.com/read/28676523/macrophage-11%C3%AE-hsd-1-deficiency-promotes-inflammatory-angiogenesis
#19
Zhenguang Zhang, Agnes E Coutinho, Tak Yung Man, Tiina M J Kipari, Patrick W F Hadoke, Donald M Salter, Jonathan R Seckl, Karen E Chapman
11β-Hydroxysteroid dehydrogenase-1 (11β-HSD1) predominantly converts inert glucocorticoids into active forms, thereby contributing to intracellular glucocorticoid levels. 11β-HSD1 is dynamically regulated during inflammation, including in macrophages where it regulates phagocytic capacity. The resolution of inflammation in some disease models including inflammatory arthritis is impaired by 11β-HSD1 deficiency or inhibition. However, 11β-HSD1 deficiency/inhibition also promotes angiogenesis, which is beneficial in mouse models of surgical wound healing, myocardial infarction or obesity...
September 2017: Journal of Endocrinology
https://www.readbyqxmd.com/read/28663252/glucose-transporter-3-potentiates-degranulation-and-is-required-for-platelet-activation
#20
Trevor P Fidler, Elizabeth A Middleton, Jesse W Rowley, Luc H Boudreau, Robert A Campbell, Rhonda Souvenir, Trevor Funari, Nicolas Tessandier, Eric Boilard, Andrew S Weyrich, E Dale Abel
OBJECTIVE: On activation, platelets increase glucose uptake, glycolysis, and glucose oxidation and consume stored glycogen. This correlation between glucose metabolism and platelet function is not well understood and even less is known about the role of glucose metabolism on platelet function in vivo. For glucose to enter a cell, it must be transported through glucose transporters. Here we evaluate the contribution of GLUT3 (glucose transporter 3) to platelet function to better understand glucose metabolism in platelets...
September 2017: Arteriosclerosis, Thrombosis, and Vascular Biology
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