Department of Analytical Chemistry, Medical University of Bialystok, 15-222 Bialystok, Poland.
Laboratory for Oxidative Stress, Rudjer Boskovic Institute, 10000 Zagreb, Croatia.
Int J Mol Sci. 2021 Jan 13;22(2):723. doi: 10.3390/ijms22020723.
Autoimmune diseases, including psoriasis, systemic lupus erythematosus (SLE), and rheumatic arthritis (RA), are caused by a combination of environmental and genetic factors that lead to overactivation of immune cells and chronic inflammation. Since oxidative stress is a common feature of these diseases, which activates leukocytes to intensify inflammation, antioxidants could reduce the severity of these diseases. In addition to activating leukocytes, oxidative stress increases the production of lipid mediators, notably of endocannabinoids and eicosanoids, which are products of enzymatic lipid metabolism that act through specific receptors. Because the anti-inflammatory CB2 receptors are the predominant cannabinoid receptors in leukocytes, endocannabinoids are believed to act as anti-inflammatory factors that regulate compensatory mechanisms in autoimmune diseases. While administration of eicosanoids in vitro leads to the differentiation of lymphocytes into T helper 2 (Th2) cells, eicosanoids are also necessary for the different0iation of Th1 and Th17 cells. Therefore, their antagonists and/or the genetic deletion of their receptors abolish inflammation in animal models of psoriasis-RA and SLE. On the other hand, products of non-enzymatic lipid peroxidation, especially acrolein and 4-hydroxynonenal-protein adducts, mostly generated by an oxidative burst of granulocytes, may enhance inflammation and even acting as autoantigens and extracellular signaling molecules in the vicious circle of autoimmune diseases.
自身免疫性疾病，包括银屑病、系统性红斑狼疮（SLE）和类风湿关节炎（RA），是由环境和遗传因素共同作用引起的，这些因素导致免疫细胞过度激活和慢性炎症。由于氧化应激是这些疾病的共同特征，它会激活白细胞以加剧炎症，抗氧化剂可以减轻这些疾病的严重程度。除了激活白细胞，氧化应激还会增加脂质介质的产生，特别是内源性大麻素和类花生酸，它们是酶促脂质代谢的产物，通过特定的受体发挥作用。由于白细胞中主要的大麻素受体是抗炎性的 CB2 受体，因此内源性大麻素被认为是调节自身免疫性疾病代偿机制的抗炎因子。虽然外源性给予类花生酸可导致淋巴细胞分化为辅助性 T 细胞 2（Th2）细胞，但类花生酸对于 Th1 和 Th17 细胞的分化也是必需的。因此，在银屑病-RA 和 SLE 的动物模型中，它们的拮抗剂和/或受体的基因缺失可消除炎症。另一方面，非酶促脂质过氧化产物，特别是丙烯醛和 4-羟基壬烯醛-蛋白质加合物，主要由粒细胞的氧化爆发产生，可能会增强炎症反应，甚至作为自身抗原和细胞外信号分子，在自身免疫性疾病的恶性循环中发挥作用。
