Autocrine and paracrine regulation of lymphocyte CB2 receptor expression by TGF-beta. |
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| Authors: | Brian Gardner Li X Zu Sherven Sharma Qian Liu Alexandros Makriyannis Donald P Tashkin Steven M Dubinett |
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| Institution: | Pulmonary Immunology Laboratory, Division of Pulmonary and Critical Care Medicine, 37-131 CHS, UCLA School of Medicine, Los Angeles, California 90073, USA. |
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| 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. |
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| Keywords: | T lymphocytes G proteins cytokines |
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