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https://www.readbyqxmd.com/read/27913299/the-inhibitory-effect-of-beta-lapachone-on-rankl-induced-osteoclastogenesis
#1
Dong Ryun Gu, Joon No Lee, Gi-Su Oh, Hyung Jin Kim, Min Seuk Kim, Seoung Hoon Lee
β-lapachone (β-L) is a substrate of reduced nicotinamide adenine dinucleotide (NADH): quinone oxidoreductase 1 (NQO1). NQO1 reduces quinones to hydroquinones using NADH as an electron donor and consequently increases the intracellular NAD+/NADH ratio. The activation of NQO1 by β-L has beneficial effects on several metabolic syndromes, such as obesity, hypertension, and renal injury. However, the effect of β-L on bone metabolism remains unclear. Here, we show that β-L might be a potent inhibitor of receptor activator of nuclear factor-κB ligand (RANKL)-induced osteoclastogenesis...
November 30, 2016: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/27908288/granulocyte-macrophage-colony-stimulating-factor-receptor-%C3%AE-expression-and-its-targeting-in-antigen-induced-arthritis-and-inflammation
#2
Andrew D Cook, Cynthia Louis, Matthew J Robinson, Reem Saleh, Matthew A Sleeman, John A Hamilton
BACKGROUND: Blockade of granulocyte macrophage colony-stimulating factor (GM-CSF) and its receptor (GM-CSFRα) is being successfully tested in trials in rheumatoid arthritis (RA) with clinical results equivalent to those found with neutralization of the current therapeutic targets, TNF and IL-6. To explore further the role of GM-CSF as a pro-inflammatory cytokine, we examined the effect of anti-GM-CSFRα neutralization on myeloid cell populations in antigen-driven arthritis and inflammation models and also compared its effect with that of anti-TNF and anti-IL-6...
December 1, 2016: Arthritis Research & Therapy
https://www.readbyqxmd.com/read/27891058/ido2-a-pathogenic-mediator-of-inflammatory-autoimmunity
#3
REVIEW
Lauren M F Merlo, Laura Mandik-Nayak
Indoleamine 2,3-dioxygenase 2 (IDO2), a homolog of the better-studied tryptophan-catabolizing enzyme IDO1, is an immunomodulatory molecule with potential effects on various diseases including cancer and autoimmunity. Here, we review what is known about the direct connections between IDO2 and immune function, particularly in relationship to autoimmune inflammatory disorders such as rheumatoid arthritis and lupus. Accumulating evidence indicates that IDO2 acts as a pro-inflammatory mediator of autoimmunity, with a functional phenotype distinct from IDO1...
2016: Clinical Medicine Insights. Pathology
https://www.readbyqxmd.com/read/27883001/psoriasis
#4
Jacqueline E Greb, Ari M Goldminz, James T Elder, Mark G Lebwohl, Dafna D Gladman, Jashin J Wu, Nehal N Mehta, Andrew Y Finlay, Alice B Gottlieb
Psoriasis is a chronic, immune-mediated disorder with cutaneous and systemic manifestations and substantial negative effects on patient quality of life. Psoriasis has a strong, albeit polygenic, genetic basis. Whereas approximately half of the accountable genetic effect of psoriasis maps to the major histocompatibility complex, >70 other loci have been identified, many of which implicate nuclear factor-κB, interferon signalling and the IL-23-IL-23 receptor axis. Psoriasis pathophysiology is characterized by abnormal keratinocyte proliferation and immune cell infiltration in the dermis and epidermis involving the innate and adaptive immune systems, with important roles for dendritic cells and T cells, among other cells...
November 24, 2016: Nature Reviews. Disease Primers
https://www.readbyqxmd.com/read/27861821/effects-of-c2ta-genetic-polymorphisms-on-mhc-class-ii-expression-and-autoimmune-diseases
#5
Anthony Cy Yau, Fredrik Piehl, Tomas Olsson, Rikard Holmdahl
Antigen presentation by the major histocompatibility complex class II (MHC-II) to CD4(+) T cells is important in adaptive immune responses. The class II transactivator (CIITA in human and C2TA in mouse) is the master regulator of MHC-II gene expression. It coordinates the transcription factors necessary for the transcription of MHC-II molecules. In humans, genetic variation in C2ta has been associated with differential expression of MHC-II and susceptibility to autoimmune diseases. Here we made use of a C2ta congenic mouse strain (expressing MHC-II haplotype H-2(q) ) to investigate the effect of the natural genetic polymorphisms in type I promoter of C2ta on MHC-II expression and function...
November 15, 2016: Immunology
https://www.readbyqxmd.com/read/27826300/treatment-with-dexamethasone-and-monophosphoryl-lipid-a-removes-disease-associated-transcriptional-signatures-in-monocyte-derived-dendritic-cells-from-rheumatoid-arthritis-patients-and-confers-tolerogenic-features
#6
Paulina A García-González, Katina Schinnerling, Alejandro Sepúlveda-Gutiérrez, Jaxaira Maggi, Lorena Hoyos, Rodrigo A Morales, Ahmed M Mehdi, Hendrik J Nel, Lilian Soto, Bárbara Pesce, María Carmen Molina, Miguel Cuchacovich, Milton L Larrondo, Óscar Neira, Diego Francisco Catalán, Catharien M Hilkens, Ranjeny Thomas, Ricardo A Verdugo, Juan C Aguillón
Tolerogenic dendritic cells (TolDCs) are promising tools for therapy of autoimmune diseases, such as rheumatoid arthritis (RA). Here, we characterize monocyte-derived TolDCs from RA patients modulated with dexamethasone and activated with monophosphoryl lipid A (MPLA), referred to as MPLA-tDCs, in terms of gene expression, phenotype, cytokine profile, migratory properties, and T cell-stimulatory capacity in order to explore their suitability for cellular therapy. MPLA-tDCs derived from RA patients displayed an anti-inflammatory profile with reduced expression of co-stimulatory molecules and high IL-10/IL-12 ratio, but were capable of migrating toward the lymphoid chemokines CXCL12 and CCL19...
2016: Frontiers in Immunology
https://www.readbyqxmd.com/read/27799933/ectopic-lymphoid-structures-powerhouse-of-autoimmunity
#7
REVIEW
Elisa Corsiero, Alessandra Nerviani, Michele Bombardieri, Costantino Pitzalis
Ectopic lymphoid structures (ELS) often develop at sites of inflammation in target tissues of autoimmune diseases, such as rheumatoid arthritis, Sjögren's syndrome, multiple sclerosis, myasthenia gravis, and systemic lupus erythematosus. ELS are characterized by the formation of organized T/B cells aggregates, which can acquire follicular dendritic cells network supporting an ectopic germinal center response. In this review, we shall summarize the mechanisms that regulate the formation of ELS in tertiary lymphoid organs, with particular emphasis on the role of lymphoid chemokines in both formation and maintenance of ELS, the role of emerging positive and negative regulators of ELS development and function, including T follicular helper cells and IL-27, respectively...
2016: Frontiers in Immunology
https://www.readbyqxmd.com/read/27798154/icos-ligand-triggering-impairs-osteoclast-differentiation-and-function-in-vitro-and-in-vivo
#8
Casimiro L Gigliotti, Elena Boggio, Nausicaa Clemente, Yogesh Shivakumar, Erika Toth, Daniele Sblattero, Patrizia D'Amelio, Giovanni C Isaia, Chiara Dianzani, Junji Yagi, Josè M Rojo, Annalisa Chiocchetti, Renzo Boldorini, Michela Bosetti, Umberto Dianzani
Osteoblasts, osteocytes, and osteoclasts (OCs) are involved in the bone production and resorption, which are crucial in bone homeostasis. OC hyperactivation plays a role in the exaggerated bone resorption of diseases such as osteoporosis, rheumatoid arthritis, and osteolytic tumor metastases. This work stems from the finding that OCs can express B7h (ICOS-Ligand), which is the ligand of the ICOS T cell costimulatory molecule. Because recent reports have shown that, in endothelial, dendritic, and tumor cells, B7h triggering modulates several activities of these cells, we analyzed the effect of B7h triggering by recombinant ICOS-Fc on OC differentiation and function...
October 19, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/27775097/involvement-of-p2x7-receptor-signaling-on-regulating-the-differentiation-of-th17-cells-and-type-ii-collagen-induced-arthritis-in-mice
#9
Zhi-Dan Fan, Ya-Yuan Zhang, Yi-Hong Guo, Na Huang, Hui-Hui Ma, Hui Huang, Hai-Guo Yu
Interleukin (IL)-17 producing T helper (Th17) cells are major effector cells in the pathogenesis of rheumatoid arthritis (RA). The P2X7 receptor (P2X7R) has emerged as a potential site in the regulation of inflammation in RA but little is known of its functional role on the differentiation of Th17 cells. This study investigates the in vitro and in vivo effects of P2X7R on Th17 cell differentiation during type II collagen (CII) induced experimental arthritis model. In CII-treated dendritic cells (DCs) and DC/CD4(+) T coculture system, pretreatment with pharmacological antagonists of P2X7R (Suramin and A-438079) caused strong inhibition of production of Th17-promoting cytokines (IL-1β, TGF-β1, IL-23p19 and IL-6)...
October 24, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27733758/the-danger-from-within-alarmins-in-arthritis
#10
Meriam Nefla, Dirk Holzinger, Francis Berenbaum, Claire Jacques
Alarmins (also known as danger signals) are endogenous molecules that are released to the extracellular milieu after infection or tissue damage. Extracellular alarmins interact with specific receptors expressed by cells that are engaged in host defence to stimulate signalling pathways that result in initiation of innate and adaptive immune responses, triggering inflammation or tissue repair. Alarmins are considered to be markers of destructive processes that occur in degenerative joint diseases (primarily osteoarthritis (OA)) and chronic inflammatory joint diseases (such as rheumatoid arthritis, psoriatic arthritis and spondylarthropathy)...
October 13, 2016: Nature Reviews. Rheumatology
https://www.readbyqxmd.com/read/27725312/genetic-variations-within-the-promotor-region-of-the-human-histamine-h4-receptor-gene-in-psoriasis-patients
#11
Susanne Mommert, Lisanne Ratz, Kira Herwig, Maren Rost, Ralf Gutzmer, Thomas Werfel
Environmental triggers and genetic factors are supposed to lead to complex gene expression changes in psoriasis and interact in the manifestation of the disease. The histamine H4 receptor (HRH4) is functionally expressed on Th17 cells and plasmacytoid dendritic cells (pDCs) which play a prominent role in the pathogenesis of psoriasis. On pDCs a higher basal expression level of the HRH4 in psoriasis patients compared to healthy controls has been detected. The functional relationship between predisposing genetic variations in the HRH4 gene and psoriasis is yet not known...
October 7, 2016: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/27677654/inhibition-of-cytokine-response-to-tlr-stimulation-and-alleviation-of-collagen-induced-arthritis-in-mice-by-schistosoma-japonicum-peptide-sjmhe1
#12
Xuefeng Wang, Li Li, Jun Wang, Liyang Dong, Yang Shu, Yong Liang, Liang Shi, Chengcheng Xu, Yuepeng Zhou, Yi Wang, Deyu Chen, Chaoming Mao
Helminth-derived products have recently been shown to prevent the development of inflammatory diseases in mouse models. However, most identified immunomodulators from helminthes are mixtures or macromolecules with potentially immunogenic side effects. We previously identified an immunomodulatory peptide called SJMHE1 from the HSP60 protein of Schistosoma japonicum. In this study, we assessed the ability of SJMHE1 to affect murine splenocytes and human peripheral blood mononuclear cells (PBMCs) stimulated by toll-like receptor (TLR) ligands in vitro and its treatment effect on mice with collagen-induced arthritis (CIA)...
September 28, 2016: Journal of Cellular and Molecular Medicine
https://www.readbyqxmd.com/read/27667787/tolerogenic-dendritic-cells-generated-with-dexamethasone-and-vitamin-d3-regulate-rheumatoid-arthritis-cd4-t-cells-partly-via-transforming-growth-factor-%C3%AE-1
#13
A E Anderson, D J Swan, O Y Wong, M Buck, O Eltherington, R A Harry, A M Patterson, A G Pratt, G Reynolds, J-P Doran, J A Kirby, J D Isaacs, C M U Hilkens
Tolerogenic dendritic cells (tolDC) are a new immunotherapeutic tool for the treatment of rheumatoid arthritis (RA) and other autoimmune disorders. We have established a method to generate stable tolDC by pharmacological modulation of human monocyte-derived DC. These tolDC exert potent pro-tolerogenic actions on CD4(+) T cells. Lack of interleukin (IL)-12p70 production is a key immunoregulatory attribute of tolDC but does not explain their action fully. Here we show that tolDC express transforming growth factor (TGF)-β1 at both mRNA and protein levels, and that expression of this immunoregulatory cytokine is significantly higher in tolDC than in mature monocyte-derived DC...
September 26, 2016: Clinical and Experimental Immunology
https://www.readbyqxmd.com/read/27658741/human-tolerogenic-dendritic-cells-generated-with-protein-kinase-c-inhibitor-are-optimal-for-functional-regulatory-t-cell-induction-a-comparative-study
#14
Endy Adnan, Takuya Matsumoto, Jun Ishizaki, Sachiko Onishi, Koichiro Suemori, Masaki Yasukawa, Hitoshi Hasegawa
Tolerogenic dendritic cells (tDCs) are a promising therapeutic tool for specific induction of immunological tolerance. Human tDCs can be generated ex vivo using various compounds. However, the compound(s) most suitable for clinical application remain undefined. We compared the tolerogenic properties of tDCs treated with protein kinase C inhibitor (PKCI), dexamethasone, vitamin D3 (Vit D3), rapamycin (Rapa), interleukin (IL)-10, transforming growth factor (TGF)-β, and a combination of peroxisome proliferator-activated receptor γ agonist and retinoic acid...
September 19, 2016: Clinical Immunology: the Official Journal of the Clinical Immunology Society
https://www.readbyqxmd.com/read/27647832/ido1-and-tgf-%C3%AE-mediate-protective-effects-of-ifn-%C3%AE-in-antigen-induced-arthritis
#15
Jaya Prakash Chalise, Maria Teresa Pallotta, Sudeep Chenna Narendra, Björn Carlsson, Alberta Iacono, Joanitah Namale, Louis Boon, Ursula Grohmann, Mattias Magnusson
IFN-α prevents Ag-induced arthritis (AIA), and in this study we investigated the role of IDO1 and TGF-β signaling for this anti-inflammatory property of IFN-α. Arthritis was induced by methylated BSA (mBSA) in mBSA-sensitized wild-type (WT), Ido1(-/-), or Ifnar(-/-) mice, treated or not with IFN-α or the IDO1 product kynurenine (Kyn). Enzymatic IDO1 activity, TGF-β, and plasmacytoid dendritic cells (pDC) were neutralized by 1-methyltryptophan and Abs against TGF-β and pDC, respectively. IDO1 expression was determined by RT-PCR, Western blot, and FACS, and enzymatic activity by HPLC...
September 19, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/27639185/valproic-acid-and-lithium-meditate-anti-inflammatory-effects-by-differentially-modulating-dendritic-cell-differentiation-and-function
#16
Sy-Jye Leu, Yi-Yuan Yang, Hsing-Cheng Liu, Chieh-Yu Cheng, Yu-Chen Wu, Ming-Chyi Huang, Yuen-Lun Lee, Chi-Ching Chen, Winston W Shen, Ko-Jiunn Liu
Valproic acid (VPA), with inhibition activity mainly towards histone deacetylase (HDAC) and Glycogen Synthase Kinase (GSK)-3, and lithium, with inhibition activity mainly toward GSK-3, are both prescribed in clinical as mood-stabilizers and anticonvulsants for the control of bipolar disorder. This study aims to compare the immuno-modulation activities of VPA and lithium, especially on the differentiation and functions of dendritic cells (DC). Our data show that treatment with VPA or lithium effectively alleviated the severity of collagen-induced arthritis triggered by LPS in mice...
September 17, 2016: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/27612450/increased-chemotaxis-and-activity-of-circulatory-myeloid-progenitor-cells-may-contribute-to-enhanced-osteoclastogenesis-and-bone-loss-in-the-c57bl-6-mouse-model-of-collagen-induced-arthritis
#17
M Ikić Matijašević, D Flegar, N Kovačić, V Katavić, T Kelava, A Šućur, S Ivčević, H Cvija, E Lazić Mosler, I Kalajzić, A Marušić, D Grčević
Our study aimed to determine the functional activity of different osteoclast progenitor (OCP) subpopulations and signals important for their migration to bone lesions, causing local and systemic bone resorption during the course of collagen-induced arthritis in C57BL/6 mice. Arthritis was induced with chicken type II collagen (CII), and assessed by clinical scoring and detection of anti-CII antibodies. We observed decreased trabecular bone volume of axial and appendicular skeleton by histomorphometry and micro-computed tomography as well as decreased bone formation and increased bone resorption rate in arthritic mice in vivo...
December 2016: Clinical and Experimental Immunology
https://www.readbyqxmd.com/read/27585946/neutrophil-extracellular-traps-exacerbate-th1-mediated-autoimmune-responses-in-rheumatoid-arthritis-by-promoting-dc-maturation
#18
Garyfalia Papadaki, Konstantinos Kambas, Christiana Choulaki, Katerina Vlachou, Elias Drakos, George Bertsias, Konstantinos Ritis, Dimitrios T Boumpas, Paul R Thompson, Panayotis Verginis, Prodromos Sidiropoulos
Aberrant formation of neutrophil extracellular traps (NETs) is a key feature in rheumatoid arthritis (RA) and plays a pivotal role in disease pathogenesis. However, the mechanism through which NETs shape the autoimmune response in RA remains elusive. In this study, we demonstrate that inhibition of peptidylarginine deiminases activity in collagen-induced arthritis (CIA) mouse model significantly reduces NET formation, attenuates clinical disease activity, and prevents joint destruction. Importantly, peptidylarginine deiminase 4 blocking markedly reduces the frequency of collagen-specific IFN-γ-producing T helper 1 (Th1) cells in the draining lymph nodes of immunized mice...
September 2, 2016: European Journal of Immunology
https://www.readbyqxmd.com/read/27558513/a-one-health-overview-facilitating-advances-in-comparative-medicine-and-translational-research
#19
Cheryl Stroud, Igor Dmitriev, Elena Kashentseva, Jeffrey N Bryan, David T Curiel, Hans Rindt, Carol Reinero, Carolyn J Henry, Philip J Bergman, Nicola J Mason, Josephine S Gnanandarajah, Julie B Engiles, Falon Gray, Danielle Laughlin, Anita Gaurnier-Hausser, Anu Wallecha, Margie Huebner, Yvonne Paterson, Daniel O'Connor, Laura S Treml, James P Stannard, James L Cook, Marc Jacobs, Gerald J Wyckoff, Lee Likins, Ubadah Sabbagh, Andrew Skaff, Amado S Guloy, Harlen D Hays, Amy K LeBlanc, Joan R Coates, Martin L Katz, Leslie A Lyons, Gayle C Johnson, Gary S Johnson, Dennis P O'Brien, Dongsheng Duan, James P Calvet, Barbara Gandolfi, David A Baron, Mark L Weiss, Debra A Webster, Francis N Karanu, Edward J Robb, Robert J Harman
A1 One health advances and successes in comparative medicine and translational researchCheryl StroudA2 Dendritic cell-targeted gorilla adenoviral vector for cancer vaccination for canine melanomaIgor Dmitriev, Elena Kashentseva, Jeffrey N. Bryan, David T. CurielA3 Viroimmunotherapy for malignant melanoma in the companion dog modelJeffrey N. Bryan, David Curiel, Igor Dmitriev, Elena Kashentseva, Hans Rindt, Carol Reinero, Carolyn J. HenryA4 Of mice and men (and dogs!): development of a commercially licensed xenogeneic DNA vaccine for companion animals with malignant melanomaPhilip J...
August 2016: Clinical and Translational Medicine
https://www.readbyqxmd.com/read/27481047/role-of-the-gut-microbiome-in-modulating-arthritis-progression-in-mice
#20
Xiaofei Liu, Benhua Zeng, Juan Zhang, Wenxia Li, Fangxiang Mou, Heng Wang, Qinghua Zou, Bing Zhong, Like Wu, Hong Wei, Yongfei Fang
Genetics alone cannot explain most cases of rheumatoid arthritis (RA). Thus, investigating environmental factors such as the gut microbiota may provide new insights into the initiation and progression of RA. In this study, we performed 16S rRNA sequencing to characterise the gut microbiota of DBA1 mice that did or did not develop arthritis after induction with collagen. We found that divergence in the distribution of microbiota after induction was pronounced and significant. Mice susceptible to collagen-induced arthritis (CIA) showed enriched operational taxonomic units (OTUs) affiliated with the genus Lactobacillus as the dominant genus prior to arthritis onset...
2016: Scientific Reports
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