Yuan Michael, Kiertscher Sylvia M, Cheng Qingwen, Zoumalan Richard, Tashkin Donald P, Roth Michael D
Division of Pulmonary and Critical Care Medicine, UCLA School of Medicine, Los Angeles, CA 90095-1690, USA.
J Neuroimmunol. 2002 Dec;133(1-2):124-31. doi: 10.1016/s0165-5728(02)00370-3.
Human leukocytes express cannabinoid (CB) receptors, suggesting a role for both endogenous ligands and Delta 9-tetrahydrocannabinol (THC) as immune modulators. To evaluate this, human T cells were stimulated with allogeneic dendritic cells (DC) in the presence or absence of THC (0.625-5 microg/ml). THC suppressed T cell proliferation, inhibited the production of interferon-gamma and shifted the balance of T helper 1 (Th1)/T helper 2 (Th2) cytokines. Intracellular cytokine staining demonstrated that THC reduced both the percentage and mean fluorescence intensity of activated T cells capable of producing interferon-gamma, with variable effects on the number of T cells capable of producing interleukin-4. Exposure to THC also decreased steady-state levels of mRNA encoding for Th1 cytokines, while increasing mRNA levels for Th2 cytokines. The CB2 receptor antagonist, SR144528, abrogated the majority of these effects. We conclude that cannabinoids have the potential to regulate the activation and balance of human Th1/Th2 cells by a CB2 receptor-dependent pathway.
人类白细胞表达大麻素(CB)受体,这表明内源性配体和Δ9-四氢大麻酚(THC)均作为免疫调节剂发挥作用。为对此进行评估,在有或无THC(0.625 - 5微克/毫升)的情况下,用同种异体树突状细胞(DC)刺激人类T细胞。THC抑制T细胞增殖,抑制γ干扰素的产生,并改变辅助性T细胞1(Th1)/辅助性T细胞2(Th2)细胞因子的平衡。细胞内细胞因子染色表明,THC降低了能够产生γ干扰素的活化T细胞的百分比和平均荧光强度,对能够产生白细胞介素-4的T细胞数量有不同影响。暴露于THC还降低了编码Th1细胞因子的mRNA的稳态水平,同时增加了Th2细胞因子的mRNA水平。CB2受体拮抗剂SR144528消除了这些作用中的大部分。我们得出结论,大麻素有可能通过CB2受体依赖性途径调节人类Th1/Th2细胞的活化和平衡。