| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
*
Merck Research Laboratories, Rahway, NJ 07065; and
Columbia University, New York, NY 10032
Nitric oxide is believed to be a prominent mediator of inflammation based in part on the correlative expression of the inducible nitric oxide synthase (iNOS) gene in various pathologies. The resulting high output of the highly reactive molecule nitric oxide is then believed to play an important role in the evolving inflammatory response. Studies have shown that iNOS and nitric oxide are present in the tissues of patients with multiple sclerosis (MS). In rodent models of MS, experimental autoimmune encephalomyelitis (EAE), it has been shown that nonspecific NOS inhibitors partially ameliorate the disease. To determine the importance of iNOS in this model of MS, we induced EAE in mice containing a disrupted iNOS (NOS2) gene. Surprisingly, by day 24, the NOS2 knockout mice had a greater incidence of EAE than wild-type control mice (75 vs 12%), and had a higher average severity score (2.42 vs 0.44). These differences appear to result largely from the failure of the disease to remit in NOS2 KO mice. Wild-type mice have a profound ability to reverse EAE (82%) compared with the knockout mice (19%). This result implies that iNOS may in some instances play a protective role in autoimmune-mediated tissue destruction.
This article has been cited by other articles:
|
|
 |
|
  J. Li, E. R. Ramenaden, J. Peng, H. Koito, J. J. Volpe, and P. A. Rosenberg Tumor Necrosis Factor {alpha} Mediates Lipopolysaccharide-Induced Microglial Toxicity to Developing Oligodendrocytes When Astrocytes Are Present J. Neurosci., May 14, 2008; 28(20): 5321 - 5330. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R.E. Gonsette Review: Oxidative stress and excitotoxicity: a therapeutic issue in multiple sclerosis? Multiple Sclerosis, January 1, 2008; 14(1): 22 - 34. [Abstract] [PDF]
|
|
|
|
 |
|
 Z. T. Kelleher, A. Matsumoto, J. S. Stamler, and H. E. Marshall NOS2 Regulation of NF-{kappa}B by S-Nitrosylation of p65 J. Biol. Chem., October 19, 2007; 282(42): 30667 - 30672. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. Zhu, Y. Bando, S. Xiao, K. Yang, A. C. Anderson, V. K. Kuchroo, and S. J. Khoury CD11b+Ly-6Chi Suppressive Monocytes in Experimental Autoimmune Encephalomyelitis J. Immunol., October 15, 2007; 179(8): 5228 - 5237. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. D. Ponomarev, K. Maresz, Y. Tan, and B. N. Dittel CNS-Derived Interleukin-4 Is Essential for the Regulation of Autoimmune Inflammation and Induces a State of Alternative Activation in Microglial Cells J. Neurosci., October 3, 2007; 27(40): 10714 - 10721. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. A. Dietlin, F. M. Hofman, B. T. Lund, W. Gilmore, S. A. Stohlman, and R. C. van der Veen Mycobacteria-induced Gr-1+ subsets from distinct myeloid lineages have opposite effects on T cell expansion J. Leukoc. Biol., May 1, 2007; 81(5): 1205 - 1212. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. J. Fabis, G. S. Scott, R. B. Kean, H. Koprowski, and D. C. Hooper Loss of blood-brain barrier integrity in the spinal cord is common to experimental allergic encephalomyelitis in knockout mouse models PNAS, March 27, 2007; 104(13): 5656 - 5661. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Minguela, S. Pastor, W. Mi, J. A. Richardson, and E. S. Ward Feedback Regulation of Murine Autoimmunity via Dominant Anti-Inflammatory Effects of Interferon {gamma} J. Immunol., January 1, 2007; 178(1): 134 - 144. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Ferlito, K. Irani, N. Faraday, and C. J. Lowenstein Nitric oxide inhibits exocytosis of cytolytic granules from lymphokine-activated killer cells PNAS, August 1, 2006; 103(31): 11689 - 11694. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. S. Paintlia, M. K. Paintlia, I. Singh, and A. K. Singh IL-4-Induced Peroxisome Proliferator-Activated Receptor {gamma} Activation Inhibits NF-{kappa}B Trans Activation in Central Nervous System (CNS) Glial Cells and Protects Oligodendrocyte Progenitors under Neuroinflammatory Disease Conditions: Implication for CNS-Demyelinating Diseases J. Immunol., April 1, 2006; 176(7): 4385 - 4398. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Chen, W.-h. Lee, L. Zhong, and C.-P. Liu Regulatory T Cells Can Mediate Their Function through the Stimulation of APCs to Produce Immunosuppressive Nitric Oxide J. Immunol., March 15, 2006; 176(6): 3449 - 3460. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. Giordano, D. M. Magaletti, and E. A. Clark Nitric oxide and cGMP protein kinase (cGK) regulate dendritic-cell migration toward the lymph-node-directing chemokine CCL19 Blood, February 15, 2006; 107(4): 1537 - 1545. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Yamazaki, H. Akiba, A. Koyanagi, M. Azuma, H. Yagita, and K. Okumura Blockade of B7-H1 on Macrophages Suppresses CD4+ T Cell Proliferation by Augmenting IFN-{gamma}-Induced Nitric Oxide Production J. Immunol., August 1, 2005; 175(3): 1586 - 1592. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. P. Zehntner, C. Brickman, L. Bourbonniere, L. Remington, M. Caruso, and T. Owens Neutrophils That Infiltrate the Central Nervous System Regulate T Cell Responses J. Immunol., April 15, 2005; 174(8): 5124 - 5131. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
V. Blais and S. Rivest Effects of TNF-{alpha} and IFN-{gamma} on Nitric Oxide-Induced Neurotoxicity in the Mouse Brain J. Immunol., June 1, 2004; 172(11): 7043 - 7052. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Xiong, C. Zhu, F. Li, R. Hegazi, K. He, M. Babyatsky, A. J. Bauer, and S. E. Plevy Inhibition of Interleukin-12 p40 Transcription and NF-{kappa}B Activation by Nitric Oxide in Murine Macrophages and Dendritic Cells J. Biol. Chem., March 12, 2004; 279(11): 10776 - 10783. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Monsonego, J. Imitola, V. Zota, T. Oida, and H. L. Weiner Microglia-Mediated Nitric Oxide Cytotoxicity of T Cells Following Amyloid {beta}-Peptide Presentation to Th1 Cells J. Immunol., September 1, 2003; 171(5): 2216 - 2224. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Dasgupta, Y. Zhou, M. Jana, N. L. Banik, and K. Pahan Sodium Phenylacetate Inhibits Adoptive Transfer of Experimental Allergic Encephalomyelitis in SJL/J Mice at Multiple Steps J. Immunol., April 1, 2003; 170(7): 3874 - 3882. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Liversidge, A. Dick, and S. Gordon Nitric Oxide Mediates Apoptosis Through Formation of Peroxynitrite and Fas/Fas-Ligand Interactions in Experimental Autoimmune Uveitis Am. J. Pathol., March 1, 2002; 160(3): 905 - 916. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Mazzoni, V. Bronte, A. Visintin, J. H. Spitzer, E. Apolloni, P. Serafini, P. Zanovello, and D. M. Segal Myeloid Suppressor Lines Inhibit T Cell Responses by an NO-Dependent Mechanism J. Immunol., January 15, 2002; 168(2): 689 - 695. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. A. Arnett, R. P. Hellendall, G. K. Matsushima, K. Suzuki, V. E. Laubach, P. Sherman, and J. P.-Y. Ting The Protective Role of Nitric Oxide in a Neurotoxicant- Induced Demyelinating Model J. Immunol., January 1, 2002; 168(1): 427 - 433. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F.-D. Shi, M. Flodstrom, S. H. Kim, S. Pakala, M. Cleary, H.-G. Ljunggren, and N. Sarvetnick Control of the Autoimmune Response by Type 2 Nitric Oxide Synthase J. Immunol., September 1, 2001; 167(5): 3000 - 3006. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. A. Kahn, D. C. Archer, D. P. Gold, and C. J. Kelly Adjuvant Immunotherapy Is Dependent on Inducible Nitric Oxide Synthase J. Exp. Med., June 4, 2001; 193(11): 1261 - 1268. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. S.-H. Liu, M.-L. Zhao, C. F. Brosnan, and S. C. Lee Expression of Inducible Nitric Oxide Synthase and Nitrotyrosine in Multiple Sclerosis Lesions Am. J. Pathol., June 1, 2001; 158(6): 2057 - 2066. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L.-Y. Xu, J.-S. Yang, H. Link, and B.-G. Xiao SIN-1, a Nitric Oxide Donor, Ameliorates Experimental Allergic Encephalomyelitis in Lewis Rats in the Incipient Phase: The Importance of the Time Window J. Immunol., May 1, 2001; 166(9): 5810 - 5816. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. E. Juedes and N. H. Ruddle Resident and Infiltrating Central Nervous System APCs Regulate the Emergence and Resolution of Experimental Autoimmune Encephalomyelitis J. Immunol., April 15, 2001; 166(8): 5168 - 5175. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J Drulovic, I Dujmovic, S Mesaros, T Samardzic, D Maksimovic, N Stojsavljevic, Z Levic, and M M. Stojkovic Raised cerebrospinal fluid nitrite and nitrate levels in patients with multiple sclerosis: no correlation with disease activity Multiple Sclerosis, February 1, 2001; 7(1): 19 - 22. [Abstract] [PDF]
|
|
|
|
|
|
A. Weishaupt, S. Jander, W. Bruck, T. Kuhlmann, M. Stienekemeier, T. Hartung, K. V. Toyka, G. Stoll, and R. Gold Molecular Mechanisms of High-Dose Antigen Therapy in Experimental Autoimmune Encephalomyelitis: Rapid Induction of Th1-Type Cytokines and Inducible Nitric Oxide Synthase J. Immunol., December 15, 2000; 165(12): 7157 - 7163. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. A. Kahn, D. C. Archer, and C. J. Kelly Absence of Functional Inducible NO Synthase Enhances the Efficacy of Tolerance Induced by High Dose Antigen Feeding J. Immunol., December 1, 2000; 165(11): 6116 - 6122. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C.-Q. Chu, S. Wittmer, and D. K. Dalton Failure to Suppress the Expansion of the Activated Cd4 T Cell Population in Interferon {gamma}-Deficient Mice Leads to Exacerbation of Experimental Autoimmune Encephalomyelitis J. Exp. Med., July 3, 2000; 192(1): 123 - 128. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Vermeire, L. Thielemans, P. Matthys, and A. Billiau The effects of NO synthase inhibitors on murine collagen-induced arthritis do not support a role of NO in the protective effect of IFN-{gamma} J. Leukoc. Biol., July 1, 2000; 68(1): 119 - 124. [Abstract] [Full Text]
|
|
|
|
 |
|
 D.-M. McCafferty, E. Sihota, M. Muscara, J. L. Wallace, K. A. Sharkey, and P. Kubes Spontaneously developing chronic colitis in IL-10/iNOS double-deficient mice Am J Physiol Gastrointest Liver Physiol, July 1, 2000; 279(1): G90 - G99. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. C. van der Veen, T. A. Dietlin, F. M. Hofman, L. Pen, B. H. Segal, and S. M. Holland Superoxide Prevents Nitric Oxide-Mediated Suppression of Helper T Lymphocytes: Decreased Autoimmune Encephalomyelitis in Nicotinamide Adenine Dinucleotide Phosphate Oxidase Knockout Mice J. Immunol., May 15, 2000; 164(10): 5177 - 5183. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. C. O'Brien, B. Charlton, W. B. Cowden, and D. O. Willenborg Nitric Oxide Plays a Critical Role in the Recovery of Lewis Rats from Experimental Autoimmune Encephalomyelitis and the Maintenance of Resistance to Reinduction J. Immunol., December 15, 1999; 163(12): 6841 - 6847. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. Giovannoni, N C Silver, J O'Riordan, R F Miller, S J.R. Heales, J M Land, M Elliot, M Feldmann, D H Miller, and E J Thompson Increased urinary nitric oxide metabolites in patients with multiple sclerosis correlates with early and relapsing disease Multiple Sclerosis, October 1, 1999; 5(5): 335 - 341. [Abstract] [PDF]
|
|
|
|
 |
|
 B Zingarelli, C Szabo, and A L Salzman Reduced oxidative and nitrosative damage in murine experimental colitis in the absence of inducible nitric oxide synthase Gut, August 1, 1999; 45(2): 199 - 209. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. J. Butterfield, E. P. Blankenhorn, R. J. Roper, J. F. Zachary, R. W. Doerge, J. Sudweeks, J. Rose, and C. Teuscher Genetic Analysis of Disease Subtypes and Sexual Dimorphisms in Mouse Experimental Allergic Encephalomyelitis (EAE): Relapsing/Remitting and Monophasic Remitting/Nonrelapsing EAE Are Immunogenetically Distinct J. Immunol., March 1, 1999; 162(5): 3096 - 3102. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. K. Tarrant, P. B. Silver, J. L. Wahlsten, L. V. Rizzo, C.-C. Chan, B. Wiggert, and R. R. Caspi Interleukin 12 Protects from a T Helper Type 1-mediated Autoimmune Disease, Experimental Autoimmune Uveitis, through a Mechanism Involving Interferon {gamma}, Nitric Oxide, and Apoptosis J. Exp. Med., January 18, 1999; 189(2): 219 - 230. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Bogdan The Multiplex Function of Nitric Oxide in (Auto)immunity J. Exp. Med., May 4, 1998; 187(9): 1361 - 1365. [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
