Sodium P-aminosalicylic Acid Inhibits Manganese-Induced Neuroinflammation in BV2 Microglial Cells via NLRP3-CASP1 Inflam
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Sodium P-aminosalicylic Acid Inhibits Manganese-Induced Neuroinflammation in BV2 Microglial Cells via NLRP3-CASP1 Inflammasome Pathway Yuanyuan Fang 1,2 & Dongjie Peng 1,2 & Yuan Liang 1,2 & Lili Lu 1,2 & Junyan Li 1,2 Shiyan Ou 1,2 & Shaojun Li 1,2 & Michael Aschner 3 & Yueming Jiang 1,2
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Lin Zhao 1,2
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Received: 15 July 2020 / Accepted: 2 November 2020 # Springer Science+Business Media, LLC, part of Springer Nature 2020
Abstract Background 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. Methods Microglia-like BV2 were treated with MnCl2 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. Results 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. Conclusion 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. Keywords Manganese . Sodium para-aminosalicylate . Neuroinflammation . NLRP3 inflammasome . CASP1 inflammasome . NLRP3-CASP1 pathway
Introduction Manganese (Mn) is an essential trace element that is widely distributed in the Earth’s crust and is crucial for multiple Mndependent enzyme and Mn metalloenzymes [1]. As such, Mn Yuanyuan Fang, Dongjie Peng and Yuan Liang contributed equally to this work. * Yueming Jiang [email protected] 1
Department of Toxicology, School of Public Health, Guangxi Medical University, No. 22, Shuang-yong Rd, Nanning 530021, Guangxi, China
2
Guangxi Colleges and Universities Key Laboratory of Prevention and Control of Highly Prevalent Diseases, Guangxi Medical University, Nanning, China
3
Albert Einstein College of Medicine, Bronx, NY 10461, USA
plays a key role in numerous biochemical reactions, including immune response, ATP generation, bone growth, digestion, and reproduction [2]. Additionally, Mn is an integral constituent of metalloenzymes, such as the Mn superoxide dismutase located within the mitochondria that facilitate the detoxificatio
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