Document Detail


Δ9-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:  MEDLINE    
Abstract/OtherAbstract:
Δ(9)-tetrahydrocannabinol (Δ(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) (-/-)). This study focused on the modulation of the inflammatory immune response to influenza by Δ(9)-THC and the role of CB(1) and/or CB(2) as receptor targets for Δ(9)-THC. C57Bl/6 (wild type) and CB(1) (-/-)CB(2) (-/-) mice were administered Δ(9)-THC (75 mg/kg) surrounding the intranasal instillation of A/PR/8/34 influenza virus. Three days post infection (dpi), Δ(9)-THC broadly decreased expression levels of mRNA induced by the innate immune response to influenza, suppressed the percentage of interferon-gamma (IFN-γ)-producing CD4(+) and interleukin-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. Δ(9)-THC had little effect on the expression of CD86, major histocompatibility complex I (MHC I), and MHC II by APC isolated from the lung. In vitro studies demonstrated that lipopolysaccharide (LPS)-induced maturation was suppressed by Δ(9)-THC in bone marrow-derived DC (bmDC). Furthermore, antigen-specific IFN-γ production by CD8(+) T cells after coculture was reduced by Δ(9)-THC treatment of bmDC in a CB(1)- and/or CB(2)-dependent manner. Collectively, these studies suggest that Δ(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; Research Support, N.I.H., Extramural     Date:  2012-11-14
Journal Detail:
Title:  Toxicological sciences : an official journal of the Society of Toxicology     Volume:  131     ISSN:  1096-0929     ISO Abbreviation:  Toxicol. Sci.     Publication Date:  2013 Feb 
Date Detail:
Created Date:  2013-01-23     Completed Date:  2013-08-12     Revised Date:  2014-02-04    
Medline Journal Info:
Nlm Unique ID:  9805461     Medline TA:  Toxicol Sci     Country:  United States    
Other Details:
Languages:  eng     Pagination:  419-33     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Animals
Bronchoalveolar Lavage Fluid
Coculture Techniques
Dronabinol / toxicity*
Flow Cytometry
Humans
Inflammation / immunology*
Influenza, Human / immunology*
Mice
Mice, Inbred C57BL
Receptor, Cannabinoid, CB1 / genetics,  physiology*
Receptor, Cannabinoid, CB2 / genetics,  physiology*
Grant Support
ID/Acronym/Agency:
R01-DA007908/DA/NIDA NIH HHS; R01-DA020402/DA/NIDA NIH HHS
Chemical
Reg. No./Substance:
0/Receptor, Cannabinoid, CB1; 0/Receptor, Cannabinoid, CB2; 7J8897W37S/Dronabinol
Comments/Corrections

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