Sodium P-aminosalicylic Acid Inhibits Manganese-Induced Neuroinflammation in BV2 Microglial Cells via NLRP3-CASP1 Inflammasome Pathway

Yuanyuan Fang, Dongjie Peng, Yuan Liang, Lili Lu, Junyan Li, Lin Zhao, Shiyan Ou, Shaojun Li, Michael Aschner, Yueming Jiang

Research output: Contribution to journalArticlepeer-review

2 Scopus citations

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.

Original languageEnglish (US)
JournalBiological Trace Element Research
DOIs
StateAccepted/In press - 2020

Keywords

  • CASP1 inflammasome
  • Manganese
  • NLRP3 inflammasome
  • NLRP3-CASP1 pathway
  • Neuroinflammation
  • Sodium para-aminosalicylate

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Biochemistry
  • Clinical Biochemistry
  • Biochemistry, medical
  • Inorganic Chemistry

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