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https://www.readbyqxmd.com/read/28882929/rhob-blockade-selectively-inhibits-autoantibody-production-in-autoimmune-models-of-rheumatoid-arthritis-and-lupus
#1
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 favoring the production of pathogenic versus non-pathogenic autoantibodies. 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 model of inflammatory arthritis...
September 7, 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
#2
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...
August 17, 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
#3
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
#4
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...
August 14, 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
#5
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/therapeutical-modulation-of-plasmacytoid-dendritic-cells-in-experimental-arthritis
#6
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
OBJECTIVES: The role of plasmacytoid dendritic cells (pDCs) and type I Interferons in rheumatoid arthritis (RA) remains controversial. To explore their contribution to RA pathogenesis, we induced experimental arthritis in various animal models of pDC depletion. We also monitored the effect of localized pDC recruitment and activation on joint inflammation and bone damage. METHODS: Experimental arthritis in mice was obtained by K/BxN serum transfer, heterologous collagen immunization (CIA) or in hTNF-transgenics...
August 4, 2017: Arthritis & Rheumatology
https://www.readbyqxmd.com/read/28724439/genetic-deficiency-of-wnt5a-diminishes-disease-severity-in-a-murine-model-of-rheumatoid-arthritis
#7
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
#8
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
#9
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
https://www.readbyqxmd.com/read/28511285/association-of-increased-f4-80-high-macrophages-with-suppression-of-serum-transfer-arthritis-in-mice-with-reduced-flip-in-myeloid-cells
#10
Qi-Quan Huang, Robert Birkett, Renee E Doyle, G Kenneth Haines, Harris Perlman, Bo Shi, Philip Homan, Lianping Xing, Richard M Pope
OBJECTIVE: Macrophages are critical in the pathogenesis of rheumatoid arthritis (RA). We recently demonstrated that FLIP is necessary for the differentiation and/or survival of macrophages. We also showed that FLIP is highly expressed in RA synovial macrophages. This study was undertaken to determine if a reduction in FLIP in mouse macrophages reduces synovial tissue macrophages and ameliorates serum-transfer arthritis. METHODS: Mice with Flip deleted in myeloid cells (Flip(f/f) LysM(c/+) mice) and littermate controls were used...
September 2017: Arthritis & Rheumatology
https://www.readbyqxmd.com/read/28449847/loss-of-wdfy3-ameliorates-severity-of-serum-transfer-induced-arthritis-independently-of-autophagy
#11
Dennis J Wu, Iannis E Adamopoulos
WDFY3 is a master regulator of selective autophagy that we recently showed to interact with TRAF6 and augment RANKL-induced osteoclastogenesis in vitro and in vivo via the NF-κB pathway. Since the NF-κB pathway plays a major role in inflammation herein, we investigate the role of WDFY3 in an arthritis animal model. Our data show that WDFY3 conditional knockout mice (Wdfy3(loxP/loxP)-LysM-Cre+) were protected in the K/BxN serum transfer-induced arthritis animal model. These effects were independent of alterations in starvation-induced autophagy as evidenced by Western blot analysis of the autophagy marker LC3, autophagosome formation in osteoclast precursors and lysosome formation in osteoclasts derived from WDFY3-cKO mice compared to controls...
June 2017: Cellular Immunology
https://www.readbyqxmd.com/read/28288964/il-38-overexpression-induces-anti-inflammatory-effects-in-mice-arthritis-models-and-in-human-macrophages-in-vitro
#12
Marie-Astrid Boutet, Aurélie Najm, Géraldine Bart, Régis Brion, Sophie Touchais, Valérie Trichet, Pierre Layrolle, Cem Gabay, Gaby Palmer, Frédéric Blanchard, Benoit Le Goff
OBJECTIVES: Interleukin (IL)-38 is a newly characterised cytokine that belongs to the IL-1 family. This cytokine is expressed in the rheumatoid arthritis (RA) synovial tissue and IL-38 deficient mice have exacerbated arthritis. Here, we analysed the effect of IL-38 overexpression in the joints of arthritic mice, in human macrophages and synovial fibroblasts in vitro. METHODS: Articular injections of an adeno-associated virus (AAV) 2/8 encoding IL-38 were performed in collagen-induced arthritis (CIA), K/BxN serum transfer-induced arthritis (STIA) and antigen-induced arthritis (AIA) in mice...
July 2017: Annals of the Rheumatic Diseases
https://www.readbyqxmd.com/read/28235865/deficiency-in-il-1-receptor-type-2-aggravates-k-bxn-serum-transfer-induced-arthritis-in-mice-but-has-no-impact-on-systemic-inflammatory-responses
#13
Praxedis Martin, Gaby Palmer, Emiliana Rodriguez, Christian Alexander Seemayer, Jennifer Palomo, Dominique Talabot-Ayer, Cem Gabay
The biological activity of IL-1 is tightly regulated by the specific receptor antagonist (IL-1Ra) and the decoy receptor IL-1 receptor type 2 (IL-1R2). The role of IL-1Ra has been well demonstrated in IL-1Ra-deficient mice. In contrast, the role of endogenous IL-1R2 remains widely unknown. To define the functional role of endogenous IL-1R2 in the K/BxN serum transfer arthritis model and in IL-1β- or LPS-induced systemic inflammation in vivo, IL-1R2(-/-) mice were created and compared with wild type mice. IL-1R2(-/-) mice bred habitually and exhibited a normal phenotype...
April 1, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28179509/iga-coated-e-coli-enriched-in-crohn-s-disease-spondyloarthritis-promote-th17-dependent-inflammation
#14
Monica Viladomiu, Charles Kivolowitz, Ahmed Abdulhamid, Belgin Dogan, Daniel Victorio, Jim G Castellanos, Viola Woo, Fei Teng, Nhan L Tran, Andrew Sczesnak, Christina Chai, Myunghoo Kim, Gretchen E Diehl, Nadim J Ajami, Joseph F Petrosino, Xi K Zhou, Sergio Schwartzman, Lisa A Mandl, Meira Abramowitz, Vinita Jacob, Brian Bosworth, Adam Steinlauf, Ellen J Scherl, Hsin-Jung Joyce Wu, Kenneth W Simpson, Randy S Longman
Peripheral spondyloarthritis (SpA) is a common extraintestinal manifestation in patients with active inflammatory bowel disease (IBD) characterized by inflammatory enthesitis, dactylitis, or synovitis of nonaxial joints. However, a mechanistic understanding of the link between intestinal inflammation and SpA has yet to emerge. We evaluated and functionally characterized the fecal microbiome of IBD patients with or without peripheral SpA. Coupling the sorting of immunoglobulin A (IgA)-coated microbiota with 16S ribosomal RNA-based analysis (IgA-seq) revealed a selective enrichment in IgA-coated Escherichia coli in patients with Crohn's disease-associated SpA (CD-SpA) compared to CD alone...
February 8, 2017: Science Translational Medicine
https://www.readbyqxmd.com/read/28130500/synthetic-retinoid-am80-ameliorates-lung-and-arthritic-autoimmune-responses-by-inhibiting-t-follicular-helper-and-th17-cell-responses
#15
Debdut Naskar, Fei Teng, Krysta M Felix, C Pierce Bradley, Hsin-Jung Joyce Wu
Rheumatoid arthritis is an autoimmune disorder that affects the joints and other organs. Pulmonary complications contribute significantly to rheumatoid arthritis mortality. Retinoic acid and its synthetic compound AM80 play roles in immunoregulation but their effect on mucosal autoimmunity remains largely unknown. T follicular helper (Tfh) and Th17 cells are known to promote inflammation and autoantibody production. Using the K/BxN autoimmune arthritis model, we elucidate a novel mechanism whereby oral AM80 administration suppressed lung mucosa-associated Tfh and autoantibody responses by increasing the gut-homing α4β7 integrin expression on Tfh cells...
March 1, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28067251/analgesic-and-anti-inflammatory-effects-of-the-novel-semicarbazide-sensitive-amine-oxidase-inhibitor-szv-1287-in-chronic-arthritis-models-of-the-mouse
#16
Ádám Horváth, Awt Menghis, Bálint Botz, Éva Borbély, Ágnes Kemény, Valéria Tékus, Janka Zsófia Csepregi, Attila Mócsai, Tamás Juhász, Róza Zákány, Dóra Bogdán, Péter Mátyus, Julie Keeble, Erika Pintér, Zsuzsanna Helyes
Semicarbazide-sensitive amine oxidase (SSAO) catalyses oxidative deamination of primary amines. Since there is no data about its function in pain and arthritis mechanisms, we investigated the effects of our novel SSAO inhibitor SzV-1287 in chronic mouse models of joint inflammation. Effects of SzV-1287 (20 mg/kg i.p./day) were investigated in the K/BxN serum-transfer and complete Freund's adjuvant (CFA)-evoked active immunization models compared to the reference SSAO inhibitor LJP-1207. Mechanonociception was assessed by aesthesiometry, oedema by plethysmometry, clinical severity by scoring, joint function by grid test, myeloperoxidase activity by luminescence, vascular leakage by fluorescence in vivo imaging, histopathological changes by semiquantitative evaluation, and cytokines by Luminex assay...
January 9, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28035212/interleukin-17-expressing-innate-synovial-cells-drive-k-bxn-serum-induced-arthritis
#17
Wang Shik Cho, Eunkyeong Jang, Ho-Youn Kim, Jeehee Youn
K/BxN serum can induce arthritis in normal mice because of abundant autoantibodies that trigger an innate inflammatory response in joints. To determine whether IL-17 is involved in the pathogenesis of serum-induced arthritis, we injected wild-type and IL-17(-/-) mice with K/BxN serum and evaluated them for signs of arthritis. Unlike wild-type mice, IL-17(-/-) mice did not show any signs of arthritis. IL-17 was produced predominantly by CD3(-) CD4(-) γδTCR(-) NK1.1(-) Sca1(int) Thy1(hi) cells residing in the inflamed synovial tissue...
December 2016: Immune Network
https://www.readbyqxmd.com/read/27995997/tiarp-attenuates-autoantibody-mediated-arthritis-via-the-suppression-of-neutrophil-migration-by-reducing-cxcl2-cxcr2-and-il-6-expression
#18
Asuka Inoue, Isao Matsumoto, Yuki Tanaka, Naoto Umeda, Chinatsu Takai, Hoshimi Kawaguchi, Hiroshi Ebe, Hiroto Yoshida, Yoshihiro Matsumoto, Seiji Segawa, Satoru Takahashi, Takayuki Sumida
TNFα-induced adipose-related protein (TIARP) is a six-transmembrane protein expressed on macrophages, neutrophils and synoviocytes. We reported recently that mice deficient in TIARP (TIARP(-/-)) spontaneously develop arthritis and are highly susceptible to collagen-induced arthritis (CIA) with enhanced interleukin (IL)-6 production. However, the effects of TIARP on neutrophils and fibroblast-like synoviocytes (FLS) have not been elucidated. We analyzed the roles of TIARP in K/BxN serum transfer model using TIARP(-/-) mice...
December 20, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27911839/identifying-species-of-symbiont-bacteria-from-the-human-gut-that-alone-can-induce-intestinal-th17-cells-in-mice
#19
Tze Guan Tan, Esen Sefik, Naama Geva-Zatorsky, Lindsay Kua, Debdut Naskar, Fei Teng, Lesley Pasman, Adriana Ortiz-Lopez, Ray Jupp, Hsin-Jung Joyce Wu, Dennis L Kasper, Christophe Benoist, Diane Mathis
Th17 cells accrue in the intestine in response to particular microbes. In rodents, segmented filamentous bacteria (SFB) induce intestinal Th17 cells, but analogously functioning microbes in humans remain undefined. Here, we identified human symbiont bacterial species, in particular Bifidobacterium adolescentis, that could, alone, induce Th17 cells in the murine intestine. Similar to SFB, B. adolescentis was closely associated with the gut epithelium and engendered cognate Th17 cells without attendant inflammation...
December 13, 2016: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/27779240/specificity-evaluation-and-disease-monitoring-in-arthritis-imaging-with-complement-receptor-of-the-ig-superfamily-targeting-nanobodies
#20
Fang Zheng, Harris Perlman, Patrick Matthys, Yurong Wen, Tony Lahoutte, Serge Muyldermans, Shemin Lu, Patrick De Baetselier, Steve Schoonooghe, Nick Devoogdt, Geert Raes
Single-photon emission computed tomography combined with micro-CT (SPECT/μCT) imaging using Nanobodies against complement receptor of the Ig superfamily (CRIg), found on tissue macrophages such as synovial macrophages, has promising potential to visualize joint inflammation in experimental arthritis. Here, we further addressed the specificity and assessed the potential for arthritis monitoring. Signals obtained with (99m)Tc-labelled NbV4m119 Nanobody were compared in joints of wild type (WT) versus CRIg(-/-) mice with collagen-induced arthritis (CIA) or K/BxN serum transfer-induced arthritis (STIA)...
October 25, 2016: Scientific Reports
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