Department of Pharmacology, Faculty of Medicine, Süleyman Demirel University, Isparta, Turkey.
Department of Medical Biology, Faculty of Medicine, Ondokuz Mayıs University, Samsun, Turkey.
J Recept Signal Transduct Res. 2021 Jun;41(3):209-216. doi: 10.1080/10799893.2020.1868510. Epub 2021 Jan 5.
Microglial antigen generation (MAG) is an essential process in regulating disease states and homeostasis of the central nervous system. MAG is considered as responsible autoimmune mechanism in neurodegenerative diseases such as Alzheimer's, Parkinson's, and Huntington's diseases. Neuroprotective and regulator effects of cannabinoid receptors on these disease states and modulation with pharmacological agents are urgent subjects in recent decades. Although different aspects of microglial immune response have been investigated, specific effects of these receptor subtypes in the MAG are still unclear. Therefore, in the current study, we have investigated the effects of CB and CB receptors on antigen generation by investigating MHC-II and its master regulator CIITA by specific cannabinoid agents (ACEA, AM-251, CP 55,940, and SR144528) in the LPS-induced BV-2 cells. Additionally, the effects of drug treatments on inflammatory status were measured by determining IL-1β, IL-6, and TNF-α levels. LPS-induced increase in MHC-II and CIITA expression was inhibited by specific CB agonist, ACEA, and nonselective cannabinoid agonist CP 55,940. A combination with specific CB antagonist AM-251 prevented these inhibitory effects of ACEA and CP 55,940 on both MHC-II and CIITA expression. Although specific CB antagonist, SR144528, also prevented the inhibitory effect of CP 55,940 on MHC-II, it did not affect CIITA expression. LPS-induced IL-1β, IL-6, and TNF-α increase both attenuated with CP 55,940 and ACEA treatments. Although both selective cannabinoid antagonists inhibited this effect, preventive effects were more dominant on CB receptors. Our results demonstrated that CB receptors majorly mediates LPS-induced MHC-II and its regulator CIITA expression in microglial cells.
小胶质细胞抗原生成（MAG）是调节中枢神经系统疾病状态和内稳态的一个必要过程。MAG 被认为是阿尔茨海默病、帕金森病和亨廷顿病等神经退行性疾病中的自身免疫机制。在最近几十年，大麻素受体对这些疾病状态的神经保护和调节作用及其与药理学制剂的调制作用是一个紧迫的课题。尽管已经研究了小胶质细胞免疫反应的不同方面，但这些受体亚型在 MAG 中的特定作用仍不清楚。因此，在目前的研究中，我们通过研究 LPS 诱导的 BV-2 细胞中特定大麻素剂（ACEA、AM-251、CP 55,940 和 SR144528）对 MHC-II 及其主调控因子 CIITA 的影响，研究了 CB 和 CB 受体对 MAG 的影响。此外，通过测定 IL-1β、IL-6 和 TNF-α 水平来测量药物处理对炎症状态的影响。特异性 CB 激动剂 ACEA 和非选择性大麻素激动剂 CP 55,940 抑制 LPS 诱导的 MHC-II 和 CIITA 表达增加。与特异性 CB 拮抗剂 AM-251 联合使用可阻止 ACEA 和 CP 55,940 对 MHC-II 和 CIITA 表达的这些抑制作用。尽管特异性 CB 拮抗剂 SR144528 也阻止了 CP 55,940 对 MHC-II 的抑制作用，但它不影响 CIITA 的表达。LPS 诱导的 IL-1β、IL-6 和 TNF-α 增加均被 CP 55,940 和 ACEA 处理减弱。尽管两种选择性大麻素拮抗剂均抑制了这种作用，但对 CB 受体的抑制作用更为明显。我们的结果表明，CB 受体主要介导 LPS 诱导的小胶质细胞中 MHC-II 和其调控因子 CIITA 的表达。
