Sodium P-aminosalicylic Acid Attenuates Manganese-Induced Neuroinflammation in BV2 Microglia by Modulating NF-κB Pathway

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.

Keywords: Manganese; NF-κB pathway; Neuroinflammation; Sodium p-aminosalicylate.