Abstract
Exposure to high levels of manganese (Mn) leads to brain Mn accumulation, and a disease referred to as manganism. Activation of microglia plays an important role in Mn-induced neuroinflammation. Sodium p-aminosalicylic acid (PAS-Na) is a non-steroidal anti-inflammatory drug that inhibits Mn-induced neuroinflammation. The aim of the current study was to explore the role of NF-κB in the protective mechanism of PAS-Na on Mn-induced neuroinflammation in BV2 microglial experimental model. We treated BV2 microglia with 200 μM Mn for 24 h followed by 48 h treatment with graded concentrations of PAS-Na, using an NF-kB inhibitor, JSH-23, as a positive control. MTT results established that 200 and 400 μM PAS-Na treatment increased the Mn-induced cell viability reduction. NF-κB (P65) mRNA expression and the phosphorylation of p65 were increased in Mn-treated BV2 cell, and suppressed by PAS-Na, analogous to the effect of JSH-23 pretreatment. Furthermore, PAS-Na significantly reduced the contents of the inflammatory cytokine TNF-α and IL-1β, both of which were increased by Mn treatment. The current results show that PAS-Na attenuated Mn-induced inflammation by abrogating the activation of the NF-κB signaling pathways and reduced the release of pro-inflammatory cytokines.
Original language | English (US) |
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Pages (from-to) | 4688-4699 |
Number of pages | 12 |
Journal | Biological Trace Element Research |
Volume | 199 |
Issue number | 12 |
DOIs | |
State | Published - Dec 2021 |
Keywords
- Manganese
- NF-κB pathway
- Neuroinflammation
- Sodium p-aminosalicylate
ASJC Scopus subject areas
- Endocrinology, Diabetes and Metabolism
- Biochemistry
- Clinical Biochemistry
- Inorganic Chemistry
- Biochemistry, medical