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{bigtriangleup}9-Tetrahydrocannabinol Impairs the Inflammatory Response to Influenza Infection: Role of Antigen Presenting Cells and the Cannabinoid Receptors 1 and 2.
MedLine Citation:
PMID:  23152191     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
△(9)-tetrahydrocannabinol (△(9)-THC) has potent immune modulatory properties and can impair pathogen-induced immune defenses, which in part have been attributed to ligation of the cannabinoid receptors 1 (CB(1)) and 2 (CB(2)). Most recently, dendritic cells (DC) were identified for their potential to enhance influenza-induced immunopathology in mice lacking CB(1) and CB(2) (CB(1)(-/-)CB(2)(-/-)). The present study focused on the modulation of the inflammatory immune response to influenza by △(9)-THC and the role of CB(1) and/or CB(2) as receptor targets for △(9)-THC. C57Bl/6 (WT) and CB(1)(-/-)CB(2)(-/-) mice were administered △(9)-THC (75 mg/kg) surrounding the intranasal instillation of A/PR/8/34 influenza virus. Three days post infection (dpi), △(9)-THC broadly decreased expression levels of mRNA induced by the innate immune response to influenza, suppressed the percentage of IFN-γ-producing CD4(+) and IL-17-producing NK1.1(+)cells, and reduced the influx of antigen presenting cells (APC), including inflammatory myeloid cells and monocytes/macrophages into the lung in a CB(1)- and/or CB(2)-dependent manner. △(9)-THC had little effect on the expression of CD86, MHC I, and MHC II by APC isolated from the lung. In vitro studies demonstrated that lipopolysaccharide (LPS)-induced maturation was suppressed by △(9)-THC in bone marrow-derived DC (bmDC). Furthermore, antigen-specific IFNγ production by CD8(+) T cells after co-culture was reduced by △(9)-THC-treatment of bmDC in a CB(1)- and/or CB(2)-dependent manner. Collectively, these studies suggest that △(9)-THC potently suppresses myeloid cell immune function, in a manner involving CB(1)- and/or CB(2), thereby impairing immune responses to influenza infection.
Authors:
Peer W F Karmaus; Weimin Chen; Robert Crawford; Barbara L F Kaplan; Norbert E Kaminski
Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-11-14
Journal Detail:
Title:  Toxicological sciences : an official journal of the Society of Toxicology     Volume:  -     ISSN:  1096-0929     ISO Abbreviation:  Toxicol. Sci.     Publication Date:  2012 Nov 
Date Detail:
Created Date:  2012-11-15     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9805461     Medline TA:  Toxicol Sci     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Affiliation:
Cell and Molecular Biology Program, Michigan State University, East Lansing, MI, 48824, USA.
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