sr-144528 and Bacterial-Infections

We have reported that injection of marijuana cannabinoids, such as Delta(9)-tetrahydrocannabinol (THC), into mice, followed by infection with Legionella pneumophila (Lp), suppresses the development of cell-mediated immunity T helper 1 (Th1) activity. These effects are accompanied by suppression of interleukin (IL)-12 and interferon (IFN) gamma production and enhancement of IL-4 production suggesting THC-induced T helper cell biasing. In the current report, other T helper cell biasing mechanisms were studied. Mice were injected with THC followed 18 h later by a challenge infection with Lp. Two-hour post-infection, spleens were removed and analyzed for mRNA to either IL-12Rbeta2 or GATA3 gene products. The results showed that THC suppressed IL-12Rbeta2 but increased GATA3. Receptor antagonists for CB1 (SR141716A, SR1) and CB2 (SR144528, SR2) were also injected to analyze the involvement of cannabinoid receptors. It was determined that SR1 attenuated the THC suppression of IL-12Rbeta2, while SR2 attenuated the increase in GATA3 mRNA. These results suggest that THC suppresses Th1 biasing activity such as IL-12Rbeta2 by a CB1 mediated mechanism and enhances the Th2 biasing activity, GATA3, by a CB2 mechanism. This dichotomy of receptor involvement might result from differential expression and/or signaling function of CB1 and CB2 on Th1 and Th2 cells.

Topics: Animals; Bacterial Infections; Camphanes; Cannabinoid Receptor Antagonists; Cells, Cultured; DNA-Binding Proteins; Dronabinol; Drug Interactions; GATA3 Transcription Factor; Interferon-gamma; Interleukin-2; Interleukin-2 Receptor beta Subunit; Legionella pneumophila; Mice; Piperidines; Psychotropic Drugs; Pyrazoles; Receptors, Cannabinoid; Receptors, Interleukin; Reverse Transcriptase Polymerase Chain Reaction; Rimonabant; RNA, Messenger; Signal Transduction; Spleen; T-Lymphocytes, Helper-Inducer; Th2 Cells; Trans-Activators