title: Autocrine and paracrine regulation of lymphocyte CB2 receptor expression by TGF-beta.
abstract: The marijuana-derived cannabinoid Delta(9)-tetrahydrocannabinol (THC) has been shown to be immunosuppressive. We report that THC induces the immunosuppressive cytokine TGF-beta by human peripheral blood lymphocytes (PBL). The ability of THC to stimulate TGF-beta production was blocked by the CB2 receptor specific antagonist SR144528 but not by the CB1 specific antagonist AM251. Furthermore, our data suggest that TGF-beta actively regulates lymphocyte CB2 receptor expression in an autocrine and paracrine manner. Whereas the addition of recombinant TGF-beta to PBL cultures downregulated CB2 receptor expression, anti-TGF-beta antibody treatment increased CB2 receptor expression. We conclude that one mechanism by which THC contributes to immune suppression is by stimulating an enhanced production of lymphocyte TGF-beta.
authors.affiliation: Pulmonary Immunology Laboratory, Division of Pulmonary and Critical Care Medicine, 37-131 CHS, UCLA School of Medicine, Los Angeles, California 90073, USA.
authors.forename: Brian
authors.initials: B
authors.lastname: Gardner
authors.forename: Li X
authors.initials: LX
authors.lastname: Zu
authors.forename: Sherven
authors.initials: S
authors.lastname: Sharma
authors.forename: Qian
authors.initials: Q
authors.lastname: Liu
authors.forename: Alexandros
authors.initials: A
authors.lastname: Makriyannis
authors.forename: Donald P
authors.initials: DP
authors.lastname: Tashkin
authors.forename: Steven M
authors.initials: SM
authors.lastname: Dubinett
mesh_terms: D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology; D019898:Autocrine Communication; D015152:Blotting, Northern; D015153:Blotting, Western; D001892:Camphanes / Q000494:pharmacology; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation; D013759:Dronabinol / Q000494:pharmacology; D004797:Enzyme-Linked Immunosorbent Assay; D019204:GTP-Binding Proteins / Q000378:metabolism; D005786:Gene Expression Regulation; D006801:Humans; D007124:Immunoenzyme Techniques; D008214:Lymphocytes / Q000378:metabolism*; D008954:Models, Biological; D019899:Paracrine Communication; D010880:Piperidines / Q000494:pharmacology; D011619:Psychotropic Drugs / Q000494:pharmacology; D011720:Pyrazoles / Q000494:pharmacology; D012313:RNA / Q000378:metabolism; D043882:Receptors, Cannabinoid; D011955:Receptors, Drug / Q000096:biosynthesis*; D011994:Recombinant Proteins / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000378:metabolism*; D015854:Up-Regulation; D010566:Virulence Factors, Bordetella / Q000494:pharmacology
chemical_list: D001892:Camphanes; D010880:Piperidines; D011619:Psychotropic Drugs; D011720:Pyrazoles; D043882:Receptors, Cannabinoid; D011955:Receptors, Drug; D011994:Recombinant Proteins; C110630:SR 144528; D016212:Transforming Growth Factor beta; D010566:Virulence Factors, Bordetella; D005576:Colforsin; C103505:AM 251; D012313:RNA; D013759:Dronabinol; D000242:Cyclic AMP; D019204:GTP-Binding Proteins; D015056:1-Methyl-3-isobutylxanthine