Document Detail

Delta9-tetrahydrocannabinol induces apoptosis in macrophages and lymphocytes: involvement of Bcl-2 and caspase-1.
MedLine Citation:
PMID:  9694974     Owner:  NLM     Status:  MEDLINE    
Apoptosis is programed cell death characterized by certain cellular changes and regulated by various gene products including Bcl-2 and caspase-1. The marijuana cannabinoid, Delta9tetrahydrocannabinol (THC), has been reported to suppress in culture the proliferation of splenocytes and increase the release of IL-1 from macrophages; however, the mechanisms of these effects remain unclear. Because cannabinoids have also been reported to induce apoptosis and because the release of IL-1 and suppression of lymphoproliferation are related to apoptosis, we tested for the induction of apoptosis by THC in murine immune cell cultures. Splenocytes cultured with Con A for up to 24 hr showed evidence of DNA fragmentation determined by gel electrophoresis, terminal deoxynucleotide transferase-mediated dUTP-fluorescein nick end labeling and 3H-thymidine labeling and THC (15-30 microM) treatment increased fragmentation under these conditions. Resident peritoneal macrophages cultured with lipopolysaccharides showed no obvious fragmentation unless they were also treated with THC. Time course studies examining DNA fragmentation and cell membrane integrity (assessed by dye exclusion) showed that fragmentation preceded membrane damage indicating that THC induced apoptosis rather than cell necrosis. In addition, THC treatment of splenocytes resulted in a decrease of Bcl-2 mRNA and protein as measured by Northern and Western blotting, respectively, and the drug induced apoptosis was blocked by the caspase inhibitor, Ac-Tyr-Val-Ala-L-aspartic acid aldehyde. These data suggest that THC treatment of cultured immune cells induces apoptosis through the regulation of Bcl-2 and caspase activity.
W Zhu; H Friedman; T W Klein
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Publication Detail:
Type:  Journal Article; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  The Journal of pharmacology and experimental therapeutics     Volume:  286     ISSN:  0022-3565     ISO Abbreviation:  J. Pharmacol. Exp. Ther.     Publication Date:  1998 Aug 
Date Detail:
Created Date:  1998-09-02     Completed Date:  1998-09-02     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  0376362     Medline TA:  J Pharmacol Exp Ther     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  1103-9     Citation Subset:  IM    
Department of Medical Microbiology and Immunology, University of South Florida, College of Medicine, Tampa, Florida 33162, USA.
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MeSH Terms
Apoptosis / drug effects*
Blotting, Northern
Blotting, Western
Caspase 1
Cysteine Endopeptidases / physiology*
DNA / biosynthesis,  isolation & purification
DNA Fragmentation
Electrophoresis, Polyacrylamide Gel
Hallucinogens / pharmacology*
Lymphocytes / drug effects*,  enzymology,  metabolism
Macrophages / drug effects*,  enzymology,  metabolism
Mice, Inbred BALB C
Proto-Oncogene Proteins c-bcl-2 / physiology*
Spectrometry, Fluorescence
Tetrahydrocannabinol / pharmacology*
Grant Support
Reg. No./Substance:
0/Hallucinogens; 0/Proto-Oncogene Proteins c-bcl-2; 1972-08-3/Tetrahydrocannabinol; 9007-49-2/DNA; EC 3.4.22.-/Cysteine Endopeptidases; EC 1

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