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"Nitric Oxide" and "Autoimmunity"

Almudena García-Ortiz, Juan M Serrador
Nitric oxide (NO) is a key messenger in the pathogenesis of inflammation, linking innate and adaptive immunity. By targeting signaling molecules, NO from inducible NO synthase (iNOS) and endothelial (e)NOS affects T helper cell differentiation and the effector functions of T lymphocytes, and is a potential target for therapeutic manipulation. In this review we discuss the regulatory actions exerted by NO on T cell functions, focusing on S-nitrosylation as an important post-translational modification by which NO acts as a signaling molecule during T cell-mediated immunity...
March 5, 2018: Trends in Molecular Medicine
Rebecca S Hesterberg, John L Cleveland, Pearlie K Epling-Burnette
The immune system is remarkably responsive to a myriad of invading microorganisms and provides continuous surveillance against tissue damage and developing tumor cells. To achieve these diverse functions, multiple soluble and cellular components must react in an orchestrated cascade of events to control the specificity, magnitude and persistence of the immune response. Numerous catabolic and anabolic processes are involved in this process, and prominent roles for l-arginine and l-glutamine catabolism have been described, as these amino acids serve as precursors of nitric oxide, creatine, agmatine, tricarboxylic acid cycle intermediates, nucleotides and other amino acids, as well as for ornithine, which is used to synthesize putrescine and the polyamines spermidine and spermine...
March 8, 2018: Medical Sciences: Open Access Journal
Ying Li, Jiaojiao Wang, Lili Yu, Kai Zhao, Biao Chen, Cuiling Li, Fan Yang, Hongfang Yuan, Huiping Zhang
PROBLEM: Prokineticin 2 (PK2), a pro-inflammatory peptide, is highly expressed in primary spermatocytes. However, systematic research on PK2 and testicular inflammation is lacking to date. METHOD OF STUDY: An experimental autoimmune orchitis (EAO) model was established to detect the expression of PK2 and its receptor (prokineticin receptor 1, PKR1) 50 and 80 days after immunization. PK2 siRNA sequence was injected into the rat rete testis to downregulate the expression of PK2...
March 8, 2018: American Journal of Reproductive Immunology: AJRI
Fang-Yuan Gong, Zheng Gong, Cui-Cui Duo, Jun Wang, Chao Hong, Xiao-Ming Gao
Calreticulin (CRT), a luminal resident calcium-binding glycoprotein of the cell, is a tumor-associated antigen involved in tumorigenesis and also an autoantigen targeted by autoantibodies found in patients with various autoimmune diseases. We have previously shown that prokaryotically expressed recombinant murine CRT (rCRT) exhibits strong stimulatory activities against monocytes/macrophages in vitro and potent immunogenicity in vivo, which is partially attributable to self-oligomerization of soluble rCRT. However, even in oligomerized form native CRT (nCRT) isolated from mouse liver is much less active than rCRT, arguing against the possibility that self-oligomerization alone would license potent pro-inflammatory properties to nCRT...
February 27, 2018: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
Alexandra Thornadtsson, Anders Lind, Tomas Weitoft, Marieann Högman
BACKGROUND: Rheumatoid arthritis (RA) is an autoimmune disorder characterized by bone and joint destruction, but other organ systems can also be involved. Recent studies have suggested that the disease may start in the lungs. Exhaled nitric oxide (FE NO) is a marker of inflammation. The aims of the study were to compare the NO parameters between subjects with RA and healthy control subjects, and to examine whether the NO parameters correlated with lung function and disease activity in the subjects with RA...
February 24, 2018: Nitric Oxide: Biology and Chemistry
Ru-Tao Liu, Min Zhang, Chun-Lin Yang, Peng Zhang, Na Zhang, Tong Du, Meng-Ru Ge, Long-Tao Yue, Xiao-Li Li, Heng Li, Rui-Sheng Duan
BACKGROUND: With the recognition of the key roles of cellular metabolism in immunity, targeting metabolic pathway becomes a new strategy for autoimmune disease treatment. Guillain-Barré syndrome (GBS) is an acute immune-mediated inflammatory demyelinating disease of the peripheral nervous system, characterized by inflammatory cell infiltration. These inflammatory cells, including activated macrophages, Th1 cells, and Th17 cells, generally undergo metabolic reprogramming and rely mainly on glycolysis to exert functions...
February 21, 2018: Journal of Neuroinflammation
Luis F Hernandez, Peter Buchwald, Midhat H Abdulreda
Metabolism of the amino acid L-arginine is implicated in many physiological and pathophysiological processes including autoimmune conditions such as type 1 diabetes (T1D). Alternate arginine metabolism through the citrulline-nitric oxide (NO) or the ornithine pathways can lead to proinflammatory or immune regulatory effects, respectively. In this report, we blocked the arginine-ornithine metabolic pathway by inhibiting the enzyme arginase-1 with Nω-hydroxy-nor-arginine (nor-NOHA) to make arginine more available to the alternate citrulline pathway for augmented NO production and increased incidence of autoimmune T1D in female non-obese diabetic (NOD) mice...
January 2018: Current Research in Diabetes & Obesity Journal
Tsunahiko Hirano, Kazuto Matsunaga
Because the pathophysiology of asthma has diverse characteristics, to manage the disease effectively, it is important for clinicians to distinguish among the clinical phenotypes. Among them, adult-onset asthma, that is, late-onset asthma (LOA), is increasing because of the aging of the population. The phenotype of LOA is largely divided into two types according to the presence or absence of eosinophilic inflammation, T-helper (Th)2- and non-Th2-associated LOA. Especially in Th2 LOA related to rhinosinusitis, as pulmonary function at onset is poor and asthma exacerbations occur frequently, it is important to detect this phenotype in the early phase by using a biomarker of Th2-type inflammation such as fractional exhaled nitric oxide (FE NO )...
2018: Journal of Asthma and Allergy
Veljko Blagojević, Vesna Kovačević-Jovanović, Ivana Ćuruvija, Raisa Petrović, Ivana Vujnović, Vesna Vujić, Stanislava Stanojević
AIMS: Some gut commensals can be protective, whereas others are implicated as necessary for development of inflammatory/autoimmune diseases. Peritoneal immune cells may play an important role in promoting autoimmunity in response to gut microbiota. This study investigated the phenotype and the function of peritoneal immune cells in the autoimmunity-resistant Albino Oxford (AO), and the autoimmunity-prone Dark Agouti (DA) rat strains upon stimulation with their own colonic E. coli or Enterococcus...
February 7, 2018: Life Sciences
Tatyana Veremeyko, Amanda W Y Yung, Marina Dukhinova, Inna S Kuznetsova, Igor Pomytkin, Alexey Lyundup, Tatyana Strekalova, Natasha S Barteneva, Eugene D Ponomarev
Although it has been demonstrated that cAMP pathway affect both adaptive and innate cell functions, the role of this pathway in the regulation of T-cell-mediated central nervous system (CNS) autoimmune inflammation, such as in experimental autoimmune encephalomyelitis (EAE), remains unclear. It is also unclear how cAMP pathway affects the function of CD4 T cells in vivo at the site of inflammation. We found that adenylyl cyclase activator Forskolin besides inhibition of functions autoimmune CD4 T cells also upregulated microRNA (miR)-124 in the CNS during EAE, which is associated with M2 phenotype of microglia/macrophages...
2018: Frontiers in Immunology
Cherry P Fernandez, Fahmida Afrin, Rochelle A Flores, Woo H Kim, Jipseol Jeong, Suk Kim, Hyun S Lillehoj, Wongi Min
As the dysregulation of IL-17 is implicated in the pathogenesis of various autoimmune and inflammatory diseases, the suppression of IL-17 production by Th2 cytokines could alleviate the development of these diseases. Previously, we confirmed that inflammatory cytokines including IL-17A are strongly associated with R. anatipestifer infection, which is one of the most important bacterial pathogens in the duck industry. Here, we found that IL-4 treatment downregulated the expression of IL-17A and IL-17F transcripts in splenic lymphocytes stimulated with R...
February 2, 2018: Molecular Immunology
Swathine Chandrashekaran, Srija Karthikeyan, Arvind Balakrishnan, Sreepriya Nair, Satheesh Kumar Kumaran Madathiparambil, Jane Jose Vattathara, Krishnakumar N Menon
Quinine dihydropteridinereductase (QDPR) is involved in the synthesis of tetradihydrobiopteridine (BH4) that serve as cofactor for many aromatic hydroxylases including induced nitric oxide synthase (NOS) leading to NO production. Increased activity of QDPR has been associated with decrease levels of TGF-β, a cytokine that regulates the immune response and that elevated levels of NO has been associated with neurodegenerative diseases. Thus, expression of QDPR in astrocytes is essential to study the pathological changes observed in many neurodegenerative disorders...
January 17, 2018: International Journal of Biological Macromolecules
Mengting Zi, Yuekang Xu
As an abundantly expressed cysteine protease inhibitor widely distributed in the organisms, cystatin C is involved in various physiological processes. Due to its relatively small molecular weight and easy detection, cystatin C is commonly used as a measure for glomerular filtration rate. In pathological conditions, however, growing evidences suggest that cystatin C is associated with various immune responses against either exogenous or endogenous antigens, which ultimately result in inflammatory autoimmune diseases or tumor development if not properly controlled...
January 17, 2018: Immunology Letters
Andrea Mancini, Michela Tantucci, Petra Mazzocchetti, Antonio de Iure, Valentina Durante, Lara Macchioni, Carmela Giampà, Alessandra Alvino, Lorenzo Gaetani, Cinzia Costa, Alessandro Tozzi, Paolo Calabresi, Massimiliano Di Filippo
During multiple sclerosis (MS), a close link has been demonstrated to occur between inflammation and neuro-axonal degeneration, leading to the hypothesis that immune mechanisms may promote neurodegeneration, leading to irreversible disease progression. Energy deficits and inflammation-driven mitochondrial dysfunction seem to be involved in this process. In this work we investigated, by the use of striatal electrophysiological field-potential recordings, if the inflammatory process associated with experimental autoimmune encephalomyelitis (EAE) is able to influence neuronal vulnerability to the blockade of mitochondrial complex IV, a crucial component for mitochondrial activity responsible of about 90% of total cellular oxygen consumption...
January 8, 2018: Neurobiology of Disease
Madeleine P J White, Gill Webster, Faith Leonard, Anne Camille La Flamme
The innate immune system plays a central role in the immune-mediated pathology of multiple sclerosis, and is a therapeutic target for progressive disease. Recently, it has been demonstrated that MIS416, a novel immunomodulatory microparticle that activates NOD-2 and TLR-9-signaling, has disease-modifying activity in multiple sclerosis models. This activity is dependent on innate IFN-γ; however, the precise immune regulatory mechanisms amplified by MIS416 have not previously been determined. Using the experimental autoimmune encephalomyelitis model, MIS416 treatment was associated with IFN-γ-dependant expansion of Treg number and increased suppressive function; however, these cells did not account for disease reduction...
January 10, 2018: Scientific Reports
Sarah Benchabane, Houda Belguendouz, Nassima Behairi, Amina Arroul-Lammali, Abdelhalim Boudjelida, Pierre Youinou, Chafia Touil-Boukoffa
Primary Sjögren's syndrome (pSS) is a systemic autoimmune disorder with a complex pathophysiology primarily affecting exocrine glands, leading to compromised secretory function. Recent studies imply that many inflammatory mediators, such as pro-inflammatory cytokines and nitric oxide, are critical in the development and perpetuation of pSS systemic manifestations. In the current study, we aimed to investigate the ex vivo immunomodulatory effect of cardamonin (C16H14O4), on pro-inflammatory cytokines, TNF-α, IL-6 and inducible nitric oxide synthase (iNOS) expression during pSS...
January 5, 2018: Immunopharmacology and Immunotoxicology
Jordan R Warford, Anna-Claire Lamport, Derek R Clements, Alicia Malone, Barry E Kennedy, Youra Kim, Shashi A Gujar, David W Hoskin, Alexander S Easton
Proteoglycans are promising therapeutic targets in Multiple Sclerosis (MS), because they regulate many aspects of the immune response. This was studied using surfen, an agent that binds both heparan sulphate proteoglycans (HSPGs) and chondroitin sulphate proteoglycans (CSPGs). Initial cell culture work on bone marrow derived macrophages (BMDMs) found that surfen reduced concentrations of the chemokines CCL2, CCL4 and CCL5, with reduced messenger (m)RNA expression for Tumor Necrosis Factor, IL-6, IL-1β and inducible nitric oxide synthase...
January 4, 2018: Acta Neuropathologica Communications
Qian Wang, Hao He, Dongwei Chen, Chao Wang, Yingping Xu, Wengang Song
Liver dendritic cells (DCs) display immunosuppressive activities and inhibit the CD4+ T cell response. The present study assessed whether and how liver DCs suppress CD8+ T cells. We found that bone marrow-derived mature DCs incubated with liver stromal cells were characterized by a longer life span, reduced CD11c, IA/IE, CD80, CD86, and CD40 expression, and increased CD11b expression. These unique liver stromal cell-educated mature DCs (LSed-DCs) stimulated CD8+ T cells to express CD25 and CD69, but inhibited their proliferation...
November 7, 2017: Oncotarget
Chenglong Liu, Jia Tao, Hui Wu, Yixin Yang, Qiang Chen, Zeyu Deng, Jiandi Liu, Changshui Xu
Diabetic neuropathic pain (DNP), one of the early symptoms of diabetic neuropathy, relates to metabolic disorders induced by high blood glucose, neurotrophic vascular ischemia and hypoxia, and autoimmune factors. This study was aimed at exploring the effects of long noncoding RNA (lncRNA) BC168687 siRNA on DNP mediated by P2X7 receptor on SGCs in DRG of rats. The mechanical withdrawal threshold (MWT) and thermal withdrawal latency (TWL) of rats, the expression levels of P2X7 mRNA and protein in the DRG, and nitric oxide (NO) in the serum were, respectively, detected in our study...
2017: BioMed Research International
Qiang Liu, Haining Li, Juan Yang, Xiaoyan Niu, Chunmei Zhao, Li Zhao, Zhenhai Wang
AIMS: Optic neuritis (ON) is an inflammatory disease of the optic nerve, which often occurs in patients with multiple sclerosis (MS) and leads to retinal ganglion cell (RGC) death and even severe visual loss. Valproic acid (VPA) is a short-chain branched fatty acid with anti-epileptic, neuro-protective and anti-inflammatory effects. Here, we examined the effects of VPA in experimental autoimmune encephalomyelitis (EAE) rats and explored the underlying mechanisms. MAIN METHODS: EAE was induced by subcutaneous injection with myelin basic protein, emulsified with complete Freund's adjuvant and Mycobacterium tuberculosis H37Ra into the Lewis rats...
December 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
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