Document Detail


Attenuation of CNS inflammatory responses by nicotine involves α7 and non-α7 nicotinic receptors.
MedLine Citation:
PMID:  20932827     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
A considerable number of in vivo studies have demonstrated that the cholinergic system can dampen the peripheral immune response, and it is thought that the α7-nicotinic acetylcholine receptor (nAChR) subtype is a key mediator of this process. The goal of the present study was to determine if nicotine modulates immunological mechanisms known to be involved in the development of experimental autoimmune encephalomyelitis (EAE), a mouse model for CNS autoimmune disease, via α7-nAChRs. Here we show that nicotine exposure attenuates EAE severity and that this effect is largely abolished in nAChR α7 subunit knock-out mice. However, nicotine exposure partially retains the ability to reduce lymphocyte infiltration into the CNS, inhibit auto-reactive T cell proliferation and helper T cell cytokine production, down-regulate co-stimulatory protein expression on myeloid cells, and increase the differentiation and recruitment of regulatory T cells, even in the absence of α7-nAChRs. Diverse effects of nicotine on effector and regulatory T cells, as well as antigen-presenting cells, may be linked to differential expression patterns of nAChR subunits across these cell types. Taken together, our data show that although α7-nAChRs indeed seem to play an important role in nicotine-conferred reduction of the CNS inflammatory response and protection against EAE, other nAChR subtypes also are involved in the anti-inflammatory properties of the cholinergic system.
Authors:
Junwei Hao; Alain R Simard; Gregory H Turner; Jie Wu; Paul Whiteaker; Ronald J Lukas; Fu-Dong Shi
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Publication Detail:
Type:  Journal Article     Date:  2010-10-13
Journal Detail:
Title:  Experimental neurology     Volume:  227     ISSN:  1090-2430     ISO Abbreviation:  Exp. Neurol.     Publication Date:  2011 Jan 
Date Detail:
Created Date:  2011-01-10     Completed Date:  2011-02-04     Revised Date:  2012-03-07    
Medline Journal Info:
Nlm Unique ID:  0370712     Medline TA:  Exp Neurol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  110-9     Citation Subset:  IM    
Copyright Information:
2010 Elsevier Inc. All rights reserved.
Affiliation:
Division of Neurology, St. Joseph's Hospital and Medical Center, Phoenix, AZ 85013, USA.
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MeSH Terms
Descriptor/Qualifier:
Animals
Antigens, CD / metabolism
Cell Differentiation / drug effects,  genetics
Cell Proliferation / drug effects
Central Nervous System / drug effects*,  immunology,  pathology
Cytokines / genetics,  metabolism
Disease Models, Animal
Encephalomyelitis, Autoimmune, Experimental / drug therapy*,  genetics,  pathology*
Flow Cytometry / methods
Gene Expression Regulation / drug effects,  genetics
Lymph Nodes / drug effects,  pathology
Magnetic Resonance Imaging / methods
Mice
Mice, Knockout
Nicotine / therapeutic use*
Nicotinic Agonists / therapeutic use*
RNA, Messenger / metabolism
Receptors, Nicotinic / deficiency,  genetics,  metabolism*
Spleen / drug effects,  pathology
Statistics, Nonparametric
T-Lymphocytes, Regulatory / drug effects,  pathology
Grant Support
ID/Acronym/Agency:
R01 AI083294-01A1/AI/NIAID NIH HHS; R01 AI083294-03/AI/NIAID NIH HHS
Chemical
Reg. No./Substance:
0/Antigens, CD; 0/Cytokines; 0/Nicotinic Agonists; 0/RNA, Messenger; 0/Receptors, Nicotinic; 0/alpha7 nicotinic acetylcholine receptor; 54-11-5/Nicotine

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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