Laboratory of Physiologic Studies, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, MD 20892-9413, USA.
Prog Lipid Res. 2011 Apr;50(2):193-211. doi: 10.1016/j.plipres.2011.01.001. Epub 2011 Feb 2.
The mammalian body has a highly developed immune system which guards against continuous invading protein attacks and aims at preventing, attenuating or repairing the inflicted damage. It is conceivable that through evolution analogous biological protective systems have been evolved against non-protein attacks. There is emerging evidence that lipid endocannabinoid signaling through cannabinoid 2 (CB₂) receptors may represent an example/part of such a protective system/armamentarium. Inflammation/tissue injury triggers rapid elevations in local endocannabinoid levels, which in turn regulate signaling responses in immune and other cells modulating their critical functions. Changes in endocannabinoid levels and/or CB₂ receptor expressions have been reported in almost all diseases affecting humans, ranging from cardiovascular, gastrointestinal, liver, kidney, neurodegenerative, psychiatric, bone, skin, autoimmune, lung disorders to pain and cancer, and modulating CB₂ receptor activity holds tremendous therapeutic potential in these pathologies. While CB₂ receptor activation in general mediates immunosuppressive effects, which limit inflammation and associated tissue injury in large number of pathological conditions, in some disease states activation of the CB₂ receptor may enhance or even trigger tissue damage, which will also be discussed alongside the protective actions of the CB₂ receptor stimulation with endocannabinoids or synthetic agonists, and the possible biological mechanisms involved in these effects.
哺乳动物的身体具有高度发达的免疫系统，可以抵御持续的入侵蛋白质攻击，并旨在预防、减轻或修复所造成的损伤。可以想象，通过进化，针对非蛋白质攻击也已经进化出类似的生物保护系统。有新的证据表明，通过大麻素 2（CB₂）受体的脂质内源性大麻素信号可能代表这种保护系统/武器库的一个例子/部分。炎症/组织损伤会迅速引起局部内源性大麻素水平升高，反过来又会调节免疫和其他细胞中的信号反应，调节它们的关键功能。在影响人类的几乎所有疾病中，包括心血管、胃肠道、肝脏、肾脏、神经退行性、精神、骨骼、皮肤、自身免疫、肺部疾病到疼痛和癌症，都报告了内源性大麻素水平和/或 CB₂ 受体表达的变化，调节 CB₂ 受体活性在这些病理中具有巨大的治疗潜力。虽然 CB₂ 受体的激活通常介导免疫抑制作用，从而限制了大量病理条件下的炎症和相关组织损伤，但在某些疾病状态下，CB₂ 受体的激活可能会增强甚至引发组织损伤，这也将与内源性大麻素或合成激动剂对 CB₂ 受体刺激的保护作用以及这些作用涉及的可能生物学机制一起进行讨论。
