Department of Toxicology, School of Public Health, Guangxi Medical University, No. 22, Shuang-yong Rd, Nanning, 530021, Guangxi, China.
Guangxi Colleges and Universities Key Laboratory of Prevention and Control of Highly Prevalent Diseases, Guangxi Medical University, Nanning, China.
Biol Trace Elem Res. 2021 Sep;199(9):3423-3432. doi: 10.1007/s12011-020-02471-7. Epub 2020 Nov 6.
Sodium p-aminosalicylic acid (PAS-Na) was reported to exhibit anti-inflammatory effect in the nervous system. However, the mechanism by which PAS-Na exhibits anti-inflammatory effects on manganese (Mn)-stimulated BV2 microglia cells remains unclear. Thus, this study investigated the role of PAS-Na in Mn-stimulated BV2 microglial cells.
Microglia-like BV2 were treated with MnCl with or without the non-steroidal anti-inflammatory drug PAS-Na for 12 or 24 h to examine cell viability using MTT; for 24 or 48 h to examine levels of NLRP3, CASP1, IL-1β, and IL-18 mRNA using Real-Time quantitative PCR; for 48 h to examine levels of NLRP3 and CASP1 inflammasomes, measured by western blot analysis; and for 48 h to examine levels of inflammatory cytokines, measured by enzyme-linked immunosorbent assay.
The MTT assay showed that PAS-Na produced significant neuroprotective effect by preventing Mn-induced inflammation in BV2 microglial cells. PAS-Na significantly concentration and time dependently inhibited Mn-induced production of NLRP3, CASP1, IL-1β, and IL-18.
Taken together, our results suggest that PAS-Na exerts anti-inflammatory effects in Mn-stimulated BV2 microglial cells via downregulation of NLRP3, CASP1, IL-1β, and I L-18. Furthermore, a high concentration and prolonged PAS-Na treatment appear necessary for its therapeutic efficacy. Taken together, we conclude that PAS-Na affords therapeutic efficacy in mitigating neurological conditions associated with neuroinflammation.
对氨基水杨酸钠（PAS-Na）已被报道在神经系统中具有抗炎作用。然而，PAS-Na 对锰（Mn）刺激的 BV2 小胶质细胞发挥抗炎作用的机制尚不清楚。因此，本研究探讨了 PAS-Na 在 Mn 刺激的 BV2 小胶质细胞中的作用。
用 MnCl2 处理小胶质细胞样 BV2 细胞，并用或不用非甾体抗炎药 PAS-Na 处理 12 或 24 h，用 MTT 法检测细胞活力；用 Real-Time qPCR 检测 NLRP3、CASP1、IL-1β 和 IL-18 mRNA 的水平；用 Western blot 分析检测 NLRP3 和 CASP1 炎性小体的水平；用酶联免疫吸附试验检测炎症细胞因子的水平。
MTT 检测表明，PAS-Na 通过预防 Mn 诱导的 BV2 小胶质细胞炎症，产生显著的神经保护作用。PAS-Na 显著浓度和时间依赖性抑制 Mn 诱导的 NLRP3、CASP1、IL-1β 和 IL-18 的产生。
综上所述，我们的结果表明，PAS-Na 通过下调 NLRP3、CASP1、IL-1β 和 IL-18，在 Mn 刺激的 BV2 小胶质细胞中发挥抗炎作用。此外，高浓度和延长的 PAS-Na 治疗似乎是其治疗效果所必需的。综上所述，我们得出结论，PAS-Na 在减轻与神经炎症相关的神经疾病方面具有治疗效果。
