Yuanyuan Fang1,2, Dongjie Peng1,2, Yuan Liang1,2, Lili Lu1,2, Junyan Li1,2, Lin Zhao1,2, Shiyan Ou1,2, Shaojun Li1,2, Michael Aschner3, Yueming Jiang4,5. 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. 4. Department of Toxicology, School of Public Health, Guangxi Medical University, No. 22, Shuang-yong Rd, Nanning, 530021, Guangxi, China. ymjianggxmu@163.com. 5. Guangxi Colleges and Universities Key Laboratory of Prevention and Control of Highly Prevalent Diseases, Guangxi Medical University, Nanning, China. ymjianggxmu@163.com.
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.
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.
Authors: Omamuyovwi M Ijomone; Oritoke M Aluko; Comfort O A Okoh; Airton Cunha Martins; Michael Aschner Journal: J Trace Elem Med Biol Date: 2019-08-22 Impact factor: 3.849
Authors: Alexey A Tinkov; Monica M B Paoliello; Aksana N Mazilina; Anatoly V Skalny; Airton C Martins; Olga N Voskresenskaya; Jan Aaseth; Abel Santamaria; Svetlana V Notova; Aristides Tsatsakis; Eunsook Lee; Aaron B Bowman; Michael Aschner Journal: Int J Mol Sci Date: 2021-04-28 Impact factor: 5.923