Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 2 de 2
Filter
Add more filters










Database
Language
Publication year range
1.
PLoS One ; 6(3): e17849, 2011 Mar 25.
Article in English | MEDLINE | ID: mdl-21464982

ABSTRACT

BACKGROUND: Experimental autoimmune encephalomyelitis (EAE) is used as an animal model for human multiple sclerosis (MS), which is an inflammatory demyelinating autoimmune disease of the central nervous system characterized by activation of Th1 and/or Th17 cells. Human autoimmune diseases can be either exacerbated or suppressed by infectious agents. Recent studies have shown that regulatory T cells play a crucial role in the escape mechanism of Plasmodium spp. both in humans and in experimental models. These cells suppress the Th1 response against the parasite and prevent its elimination. Regulatory T cells have been largely associated with protection or amelioration in several autoimmune diseases, mainly by their capacity to suppress proinflammatory response. METHODOLOGY/PRINCIPAL FINDINGS: In this study, we verified that CD4(+)CD25(+) regulatory T cells (T regs) generated during malaria infection (6 days after EAE induction) interfere with the evolution of EAE. We observed a positive correlation between the reduction of EAE clinical symptoms and an increase of parasitemia levels. Suppression of the disease was also accompanied by a decrease in the expression of IL-17 and IFN-γ and increases in the expression of IL-10 and TGF-ß1 relative to EAE control mice. The adoptive transfer of CD4(+)CD25(+) cells from P. chabaudi-infected mice reduced the clinical evolution of EAE, confirming the role of these T regs. CONCLUSIONS/SIGNIFICANCE: These data corroborate previous findings showing that infections interfere with the prevalence and evolution of autoimmune diseases by inducing regulatory T cells, which regulate EAE in an apparently non-specific manner.


Subject(s)
Disease Progression , Encephalomyelitis, Autoimmune, Experimental/immunology , Encephalomyelitis, Autoimmune, Experimental/parasitology , Malaria/immunology , Malaria/parasitology , Plasmodium chabaudi/immunology , T-Lymphocytes, Regulatory/immunology , Animals , Autoimmunity/immunology , Cell Survival , Cytokines/genetics , Cytokines/metabolism , Encephalomyelitis, Autoimmune, Experimental/complications , Encephalomyelitis, Autoimmune, Experimental/genetics , Gene Expression Regulation , Humans , Interleukin-2 Receptor alpha Subunit/metabolism , Malaria/complications , Malaria/genetics , Mice , Mice, Inbred C57BL
2.
J Neurochem ; 109(6): 1680-90, 2009 Jun.
Article in English | MEDLINE | ID: mdl-19457136

ABSTRACT

Ciliary neurotrophic factor (CNTF) is a multifunctional cytokine that can regulate the survival and differentiation of many types of developing and adult neurons. CNTF prevents the degeneration of motor neurons after axotomy and in mouse mutant progressive motor neuronopathy, which has encouraged trials of CNTF for human motor neuron disease. Given systemically, however, CNTF causes severe side effects, including cachexia and a marked immune response, which has limited its clinical application. The present work describes a novel approach for administering recombinant human CNTF (rhCNTF) while conserving neurotrophic activity and avoiding deleterious side effects. rhCNTF was fused to a protein transduction domain derived from the human immunodeficiency virus-1 TAT (transactivator) protein. The resulting fusion protein (TAT-CNTF) crosses the plasma membrane within minutes and displays a nuclear localization. TAT-CNTF was equipotent to rhCNTF in supporting the survival of cultured chicken embryo dorsal root ganglion neurons. Local or subcutaneous administration of TAT-CNTF, like rhCNTF rescued motor neurons from death in neonatal rats subjected to sciatic nerve transection. In contrast to subcutaneous rhCNTF, which caused a 20-30% decrease in body weight in neonatal rats between postnatal days 2 and 7 together with a considerable fat mobilization in brown adipose tissue, TAT-CNTF lacked such side effects. Together, these results indicate that rhCNTF fused with the protein transduction domain/TAT retains neurotrophic activity in the absence of CNTFs cytokine-like side effects and may be a promising candidate for the treatment of motor neuron and other neurodegenerative diseases.


Subject(s)
Ciliary Neurotrophic Factor/therapeutic use , Neuroprotective Agents/therapeutic use , Sciatic Neuropathy/drug therapy , Adipose Tissue, Brown/drug effects , Adipose Tissue, Brown/metabolism , Animals , Animals, Newborn , Axotomy/methods , Body Weight/drug effects , Cell Count/methods , Cells, Cultured , Chick Embryo , Ciliary Neurotrophic Factor/metabolism , Cricetinae , Cricetulus , Dose-Response Relationship, Drug , Ganglia, Spinal/cytology , Green Fluorescent Proteins/genetics , Humans , Motor Neurons/drug effects , Motor Neurons/physiology , Rats , Rats, Wistar , Recombinant Fusion Proteins/metabolism , Recombinant Fusion Proteins/therapeutic use , STAT3 Transcription Factor/metabolism , Sciatic Neuropathy/etiology , Sciatic Neuropathy/physiopathology , Sensory Receptor Cells/drug effects , Sensory Receptor Cells/physiology , Transduction, Genetic/methods , tat Gene Products, Human Immunodeficiency Virus/genetics , tat Gene Products, Human Immunodeficiency Virus/therapeutic use
SELECTION OF CITATIONS
SEARCH DETAIL
...