Delta 9-tetrahydrocannabinol inhibition of tumor necrosis factor-alpha: suppression of post-translational events.
Delta 9-tetrahydrocannabinol (delta 9-THC), the major psychoactive component of marijuana, has been shown to suppress macrophage soluble cytolytic activity. The purpose of this study was to determine whether delta 9-THC inhibited this function by affecting tumor necrosis factor-alpha (TNF-alpha). The RAW264.7 macrophage cell line was used as an in vitro bacterial lipopolysaccharide-inducible system for production of TNF-alpha. Macrophage-conditioned medium of RAW264.7 macrophages treated with delta 9-THC was shown to be deficient in tumoricidal activity. Immunoprecipitation experiments demonstrated that the macrophage-conditioned medium of cultures treated with drug contained lower levels of TNF-alpha. Northern analysis indicated that delta 9-THC had no effect on the levels of TNF-alpha messenger RNA. However, radiolabel pulsing and pulse-chase experiments revealed that the intracellular conversion of the 26-kD presecreted form of TNF-alpha to the 17-kD secreted form was inhibited by the drug. These results indicate that delta 9-THC suppresses soluble macrophage tumoricidal activity, at least in part, by decreasing the intracellular conversion of presecretory TNF-alpha to its 17-kD secretory form.
Fischer-Stenger
K
K
Department of Microbiology and Immunology, Medical College of Virginia/Virginia Commonwealth University, Richmond.
Dove Pettit
D A
DA
Cabral
G A
GA
D000818:Animals; D002460:Cell Line; D003470:Culture Media; D013759:Dronabinol / Q000494:pharmacology*; D015870:Gene Expression / Q000187:drug effects; D008070:Lipopolysaccharides; D008264:Macrophages / Q000187:drug effects* / Q000378:metabolism* / Q000502:physiology; D051379:Mice; D008954:Models, Biological; D011499:Protein Processing, Post-Translational / Q000187:drug effects*; D012333:RNA, Messenger / Q000187:drug effects / Q000378:metabolism; D011817:Rabbits; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism
D003470:Culture Media; D008070:Lipopolysaccharides; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D013759:Dronabinol