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"Nitric Oxide" and "Autoimmunity"

Arshad Khan, Robert L Hunter, Chinnaswamy Jagannath
Mesenchymal stem cells (MSCs) are non-hematopoietic cells that occur in almost all human tissues and can be cultured and expanded to large numbers in vitro. They secrete growth factors, cytokines, and chemokines and express Toll-like receptors on their surface, although multiple cell biological mechanisms remain unclear. MSCs are multi-potent and can differentiate into many cell types including adipocytes, neuronal cells and osteoclasts. Despite gaps in cell biology, because of their immunomodulatory and regenerative capacity, several hundred clinical trials have used MSCs for therapy of cancer, autoimmune diseases and control of inflammation during organ transplantation...
September 28, 2016: Tuberculosis
Dina S El-Agamy
OBJECTIVES: This study aimed to evaluate the potential protective effects of pirfenidone (PFD) against concanavalin A (Con A)-induced hepatitis in mice. METHODS: Autoimmune model of hepatitis was established using single intravenous injection of Con A. Mice were randomly assigned into four groups as follows: control group; Con A group; and two groups, receiving PFD in two dose levels (200, 300 mg/kg) for 5 days before Con A administration. Extent of hepatitis was studied using biochemical, histopathological and immunohistochemical estimations...
October 13, 2016: Journal of Pharmacy and Pharmacology
Ana María Vega-Letter, Mónica Kurte, Catalina Fernández-O'Ryan, Melanie Gauthier-Abeliuk, Patricia Fuenzalida, Ivón Moya-Uribe, Claudia Altamirano, Fernando Figueroa, Carlos Irarrázabal, Flavio Carrión
BACKGROUND: Recently, it has been observed that mesenchymal stem cells (MSCs) can modulate their immunoregulatory properties depending on the specific in-vitro activation of different Toll-like receptors (TLR), such as TLR3 and TLR4. In the present study, we evaluated the effect of polyinosinic:polycytidylic acid (poly(I:C)) and lipopolysaccharide (LPS) pretreatment on the immunological capacity of MSCs in vitro and in vivo. METHODS: C57BL/6 bone marrow-derived MSCs were pretreated with poly(I:C) and LPS for 1 hour and their immunomodulatory capacity was evaluated...
October 10, 2016: Stem Cell Research & Therapy
Junwei Xu, Lu Lu, Jing Lu, Jihui Xia, Hongjin Lu, Lin Yang, Wensheng Xia, Shihai Shen
BACKGROUND: Recent evidence suggests that CD200 fusion protein (CD200Fc), a CD200R1 agonist may attenuate inflammatory responses in autoimmune diseases and neuro-degeneration. While, little is known about the function of CD200Fc in cigarette smoke extract (CSE)-induced mouse Cardiac Microvascular Endothelial Cells (mCMECs). The present study was designed to elucidate the effects of CD200Fc on CSE-induced vascular endothelial barrier (VEB) dysfunction and inflammatory responses, which is a highly clinically relevant model of smoking related cardiovascular diseases...
October 3, 2016: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
Wafaa A Hewedy, Dalia K Mostafa
BACKGROUND: Cyclosporine A (CsA)-induced nephrotoxicity is a challenging problem complicating its chronic use in a large array of autoimmune diseases, as well as in organ transplantation. A considerable body of evidence points to the involvement of nitric oxide (NO) and its endogenous synthesis inhibitor, asymmetric dimethylarginine (ADMA), in CsA-induced renal and cardiovascular adverse effects. In this study, the potential of the third generation β-blocker, nebivolol, to modify the NO/ADMA system is hypothesized to play a role in protection against CsA-induced renal injury and endothelial dysfunction...
August 31, 2016: Pharmacological Reports: PR
Ayelet Kaminitz, Shifra Ash, Nadir Askenasy
As physiological pathways of intercellular communication produced by all cells, cytokines are involved in the pathogenesis of inflammatory insulitis as well as pivotal mediators of immune homeostasis. Proinflammatory cytokines including interleukins, interferons, transforming growth factor-β, tumor necrosis factor-α, and nitric oxide promote destructive insulitis in type 1 diabetes through amplification of the autoimmune reaction, direct toxicity to β-cells, and sensitization of islets to apoptosis. The concept that neutralization of cytokines may be of therapeutic benefit has been tested in few clinical studies, which fell short of inducing sustained remission or achieving disease arrest...
September 27, 2016: Clinical Reviews in Allergy & Immunology
Shinya Takahashi, Ryuta Kikuchi, Kimiharu Ambe, Toshihiro Nakagawa, Satoshi Takada, Takashi Ohno, Hiroki Watanabe
Type I diabetes, an autoimmune disease, induces insulin deficiency, which then disrupts vascular endothelial cell function, affecting blood and lymphatic vessels. Nitric oxide (NO) is an immune-induced destructive mediator in type I diabetes, and inhibition of its production promotes arteriosclerosis. In this study, lymphangiogenesis and expression of NO synthase (NOS) during the healing process after tooth extraction were investigated immunohistochemically in control (C57BL) and Akita mice as a diabetes model...
2016: Bulletin of Tokyo Dental College
Mariana Urrutia, Sebastián Fernández, Marisol González, Rodrigo Vilches, Pablo Rojas, Manuel Vásquez, Mónica Kurte, Ana María Vega-Letter, Flavio Carrión, Fernando Figueroa, Patricio Rojas, Carlos Irarrázabal, Rodrigo A Fuentealba
The neurotransmitter GABA has been recently identified as a potent immunosuppressive agent that targets both innate and adaptive immune systems and prevents disease progression of several autoimmunity models. Mesenchymal stem cells (MSCs) are self-renewing progenitor cells that differentiate into various cell types under specific conditions, including neurons. In addition, MSC possess strong immunosuppressive capabilities. Upon cytokine priming, undifferentiated MSC suppress T-cell proliferation via cell-to-cell contact mechanisms and the secretion of soluble factors like nitric oxide, prostaglandin E2 and IDO...
2016: PloS One
Doreen E Szollosi, Ola A M Ghoneim, Mohammed K Manzoor, Jyothi Dhuguru, Ivan O Edafiogho
Pro-inflammatory mediators including TNF-alpha, IL-6, and nitric oxide are important for the regulation of the immune response when an infection is present, but when overproduced, it can be responsible for the development of tissue and organ injury seen in sepsis, as well as severe asthma, and autoimmune diseases such as Crohn's disease and rheumatoid arthritis. Data from our lab to characterize the novel compound enaminone E121 have suggested that macrophages stimulated with lipopolysaccharide (LPS) release significantly decreased levels of TNF-alpha and IL-6 as measured by enzyme-linked immunosorbent assay as compared to the DMSO control group...
September 10, 2016: Inflammation
Y Hu, X Niu, G Wang, J Huang, M Liu, B Peng
Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is an independent risk factor for the development of erectile dysfunction (ED). But the molecular mechanisms underlying the relationship between CP/CPPS and ED are still unclear. The aim of this study was to investigate the effect of CP/CPPS on erectile function in a rat model and the possible mechanisms. A rat model of experimental autoimmune prostatitis (EAP) was established to mimic human CP⁄CPPS. Then twenty 2-month-old male Sprague-Dawley rats were divided into EAP group and control group...
August 27, 2016: Andrology
Chuanping Si, Ruihua Zhang, Tianshu Wu, Geming Lu, Yuan Hu, Hui Zhang, Feihong Xu, Peter Wei, Kang Chen, Hua Tang, Garabet Yeretssian, Huabao Xiong
Dendritic cells (DCs) play a pivotal role in the development of effective immune defense while avoiding detrimental inflammation and autoimmunity by regulating the balance of adaptive immunity and immune tolerance. However, the mechanisms that govern the effector and regulatory functions of DCs are incompletely understood. Here, we show that DC-derived nitric oxide (NO) controls the balance of effector and regulatory DC differentiation. Mice deficient in the NO-producing enzyme inducible nitric oxide synthase (iNOS) harbored increased effector DCs that produced interleukin-12, tumor necrosis factor (TNF) and IL-6 but normal numbers of regulatory DCs that expressed IL-10 and programmed cell death-1 (PD-1)...
August 18, 2016: Oncotarget
Emna Dabbeche-Bouricha, Luiza M Araujo, Masashi Kato, Armelle Prévost-Blondel, Henri-Jean Garchon
Mice transgenic for the RET oncogene provide a remarkable model for investigating the mechanisms underlying the promotion and the development of melanoma. This model was established on the C57BL/6 genetic background. In the present study, we investigated an effect of the strongly proinflammatory and autoimmune genetic makeup of the non-obese diabetic (NOD) strain. We bred (NODxB6)F1 mice and backcrossed them with NOD mice. F1 mice and mice at subsequent generations of backcrossing showed marked acceleration of tumor development, in particular with a more frequent and earlier extension of the primary uveal melanoma...
May 2016: Oncoimmunology
Joanna Latuskiewicz-Potemska, Antonina Chmura-Skirlinska, Ryszard J Gurbiel, Elzbieta Smolewska
Raynaud syndrome (RS) manifests as episodes of transient spasms of peripheral blood vessels, most often in response to cold. The reason of that symptom (primary RS (pRS)) usually cannot be found but may be accompanied by some autoimmune diseases (secondary RS (sRS)). In this study, we assessed microcapillary status and serum concentrations of chosen cytokines, adhesive molecules, and nitric oxide (NO) in patients with pRS and sRS in comparison with healthy children. Eighty-six patients with RS were enrolled into the study, including 52 with pRS and 34 with sRS...
August 2016: Clinical Rheumatology
Gerwyn Morris, Michael Berk, Hans Klein, Ken Walder, Piotr Galecki, Michael Maes
Nitric oxide plays an indispensable role in modulating cellular signaling and redox pathways. This role is mainly effected by the readily reversible nitrosylation of selective protein cysteine thiols. The reversibility and sophistication of this signaling system is enabled and regulated by a number of enzymes which form part of the thioredoxin, glutathione, and pyridoxine antioxidant systems. Increases in nitric oxide levels initially lead to a defensive increase in the number of nitrosylated proteins in an effort to preserve their function...
June 23, 2016: Molecular Neurobiology
Li Wang, Shengli Zhu, Gang Xu, Jian Feng, Tao Han, Fanpeng Zhao, Ying-Long She, Shi Liu, Linbai Ye, Ying Zhu
Interleukin-35 (IL-35) is a newly described member of the IL-12 family. It has been reported to inhibit inflammation and autoimmune inflammatory disease and can increase apoptotic sensitivity. Little is known about the role of IL-35 during viral infection. Herein, high levels of IL-35 were found in peripheral blood mononuclear cells and throat swabs from patients with seasonal influenza A virus (IAV) relative to healthy individuals. IAV infection of human lung epithelial and primary cells increased levels of IL-35 mRNA and protein...
August 5, 2016: Journal of Biological Chemistry
Suneetha Amara, Margaret Whalen, Venkataswarup Tiriveedhi
Macrophages play a critical role in inflammation and antigen-presentation. Abnormal macrophage function has been attributed in autoimmune diseases and cancer progression. Recent evidence suggests that high salt tissue micro-environment causes changes in macrophage activation. In our current report, we studied the role of extracellular sodium chloride on phenotype changes in peripheral circulating monocyte/macrophages collected from healthy donors. High salt (0.2 M NaCl vs basal 0.1 M NaCl) treatment resulted in a decrease in MΦ1 macrophage phenotype (CD11b(+)CD14(high)CD16(low)) from 77...
September 2016: Biochemistry and Biophysics Reports
Bojan Jevtić, Neda Djedović, Suzana Stanisavljević, Jovana Despotović, Djordje Miljković, Gordana Timotijević
Cucurbitacin E (CucE) is a highly oxidized steroid consisting of a tetracyclic triterpene. It is a member of a Cucurbitacin family of biomolecules that are predominantly found in Cucurbitaceae plants. CucE has already been identified as a potent anti-inflammatory compound. Here, its effects on CD4(+) T helper (Th) cells and macrophages, as the major encephalitogenic cells in the autoimmunity of the central nervous system, were investigated. Production of major pathogenic Th cell cytokines: interferon-gamma and interleukin-17 were inhibited under the influence of CucE...
June 22, 2016: Journal of Agricultural and Food Chemistry
Min-Jung Park, Sung-Hee Lee, Eun-Kyung Kim, Eun-Jung Lee, Sung-Hwan Park, Seung-Ki Kwok, Mi-La Cho
OBJECTIVE: This study was undertaken to assess the impact of myeloid-derived suppressor cells (MDSCs) on various B cell subsets, including regulatory B cells. Further, the potential therapeutic effects of infusion of MDSCs in an animal model of systemic lupus erythematosus (SLE) were assessed. METHODS: Splenocytes were cultured with MDSCs and the populations of various B cells and effector T cell subsets were analyzed by flow cytometry. Lupus mice (Roquin(san/san) mice) were treated intravenously with MDSCs obtained from C57BL/6 mice, and serum autoantibodies, degree of proteinuria, histologic changes in the kidney and populations of various B cell and T cell subsets in the spleen were analyzed...
May 23, 2016: Arthritis & Rheumatology
Sarah Benchabane, Abdelhalim Boudjelida, Ryma Toumi, Houda Belguendouz, Pierre Youinou, Chafia Touil-Boukoffa
Sjögren's syndrome (SS) is an autoimmune epithelitis characterized by mononuclear cell (MNC) infiltration of the lacrimal and salivary glands (SG), as well as the presence of serum autoantibodies. This condition is a growing public health concern in Algeria. Herein, we sought to determine if the levels of interleukin (IL)-6, IL-17A, and nitric oxide (NO), were correlated with the extent of MNC infiltration. The expression of inducible NO synthase (NOS2) and CD68 was measured in the SG of all patients, but not in those of the normal controls (NCs)...
September 2016: International Journal of Immunopathology and Pharmacology
Chenlu Han, Tingting Wu, Ning Na, Yang Zhao, Weiguo Li, Yong Zhao
OBJECTIVE: Myeloid-derived suppressor cells (MDSCs) play important roles in preventing graft rejection. Immunosuppressive drug cyclosporine A (CsA) is widely used in clinics to treat patients with allografts and autoimmune diseases. However, the effect of CsA on CD11b(+)Gr1(+) MDSCs has not been studied. SUBJECTS: The subjects of the study include BALB/c skin-grafted C57BL/6 mice and the in vitro MDSCs induction system. TREATMENT: Skin-grafted mice were treated with CsA (30 mg/kg, i...
September 2016: Inflammation Research: Official Journal of the European Histamine Research Society ... [et Al.]
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