P2‐198: PM2.5 INDUCES NEUROINFLAMMATION IN GLIAL CELLS: ASSOCIATION WITH TPA/PAI‐1 SYSTEM

Abstract

Particulate matter 2.5 (PM2.5) can gain access to the lungs and the circulatory system and may sequentially cross the blood brain barrier (BBB). Recent data suggested that these particles reaching the brain may cause neurological disorders including AD and PD. However, there is no study on how to prevent PM2.5-induced inflammation and neurotoxicity. In this study, we have demonstrated that PM2.5 increases the PAI-1 activity and neuroinflammation, and that natural extracts such as astaxanthin and chlorophyll can prevent the subsequent neurotoxicity, mainly based on its anti-oxidative and anti-inflammatory properties. In this regard, we examined 1) the mRNA expression of inflammatory mediators including iNOS, IL-1a, tPA, PAI-1, TNFa, c1q, TGFb and BDNF, 2) nitric oxide and reactive oxygen species production, 3) tPA and PAI-1 activity, and 4) neurite extension assay using the immunocytochemistry. We used a well-characterized Diesel particulate matter, PM2.5, from SIGMA-Aldrich. PM2.5 increased inflammatory cytokines such as IL-6 production in rat astrocytes, and PAI-1 mRNA expression activity in rat primary astrocytes. Astaxanthin attenuated PM2.5-induced increased NO and other inflammatory cytokines expressions and prevented neuronal cell death in rat primary cortical neurons. Our results show that PM2.5 activates the astrocytes through PAI-1 activation leading to neurotoxicity, and astaxanthin and chlorophyll can prevent this through the inhibition of astrocytes activation. These results demonstrate that the potential beneficial effects of astaxanthin and chlorophyll against air pollution exposure such as PM2.5.