Autocrine and paracrine regulation of lymphocyte CB2 receptor expression by TGF-β

被引:47
作者
Gardner, B
Zu, LX
Sharma, S
Liu, Q
Makriyannis, A
Tashkin, DP
Dubinett, SM
机构
[1] Univ Calif Los Angeles, Sch Med, Immunol Pulm Lab, Los Angeles, CA 90073 USA
[2] Univ Calif Los Angeles, Sch Med, Div Pulm & Crit Care Med, Los Angeles, CA 90073 USA
[3] VA W Los Angeles Healthcare Ctr, Los Angeles, CA 90073 USA
[4] Univ Connecticut, Dept Pharmaceut Sci, Storrs, CT 06269 USA
[5] Univ Connecticut, Dept Mol & Cell Biol, Storrs, CT 06269 USA
关键词
T lymphocytes; G proteins; cytokines;
D O I
10.1006/bbrc.2001.6179
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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. (C) 2002 Elsevier Science.
引用
收藏
页码:91 / 96
页数:6
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