Malfitano A M, Laezza C, Pisanti S, Gazzerro P, Bifulco M
Dipartimento di Scienze Farmaceutiche, Universitá di Salerno, Fisciano (SA), Italy.
Br J Pharmacol. 2008 Mar;153(5):1003-10. doi: 10.1038/sj.bjp.0707651. Epub 2007 Dec 24.
Rimonabant (SR141716) is the first selective cannabinoid receptor CB(1) antagonist described. Along with its anti-obesity action, emerging findings show potential anti-proliferative and anti-inflammatory action of SR141716 in several in vitro and in vivo models. In this study we have investigated the anti-proliferative and immunomodulatory effects of SR141716 in human peripheral blood mononuclear cells (PBMCs).
We have evaluated in vitro the effect of SR141716 in human PBMCs stimulated with different mitogens. Cell proliferation was assessed by (3)H-thymidine incorporation. Cell cycle, cell death and apoptosis were analysed by flow cytometry. Protein expression was investigated by Western blot.
SR141716 significantly inhibited the proliferative response of PBMCs and this effect was accompanied by block of G(1)/S phase of the cell cycle without induction of apoptosis and cell death. SR141716 used in combination with 2-methyl-arachidonyl-2'-fluoro-ethylamide (Met-F-AEA), a stable analogue of the endogenous cannabinoid anandamide, showed synergism rather than antagonism of the inhibition of cell proliferation. The immunomodulatory effects of SR141716 were associated with increased expression of IkappaB, phosphorylated AKT (p-AKT) and decreased expression of NF-kappaB, p-IkappaB, p-ERK, COX-2 and iNOS.
Our findings suggest SR141716 is a novel immunomodulatory drug with anti-inflammatory properties.
利莫那班（SR141716）是首个被描述的选择性大麻素受体CB(1)拮抗剂。除了其抗肥胖作用外，新出现的研究结果显示，SR141716在多种体外和体内模型中具有潜在的抗增殖和抗炎作用。在本研究中，我们调查了SR141716对人外周血单个核细胞（PBMCs）的抗增殖和免疫调节作用。
我们在体外评估了SR141716对用不同丝裂原刺激的人PBMCs的作用。通过³H-胸腺嘧啶核苷掺入法评估细胞增殖。通过流式细胞术分析细胞周期、细胞死亡和凋亡。通过蛋白质印迹法研究蛋白质表达。
SR141716显著抑制PBMCs的增殖反应，且该作用伴随着细胞周期G(1)/S期的阻滞，而未诱导凋亡和细胞死亡。SR141716与内源性大麻素花生四烯乙醇胺的稳定类似物2-甲基-花生四烯酰-2'-氟乙酰胺（Met-F-AEA）联合使用时，对细胞增殖抑制显示出协同作用而非拮抗作用。SR141716的免疫调节作用与IkappaB、磷酸化AKT（p-AKT）表达增加以及NF-kappaB、p-IkappaB、p-ERK、COX-2和iNOS表达降低有关。
我们的研究结果表明，SR141716是一种具有抗炎特性的新型免疫调节药物。
