Effect of Mn Fumes Inhalation on Inflammation Resolution in Microglia

Authors: Arthika Kandasamy, Vijay Muthaiah, Ayesha Jannat, Lydia Clark, Mylin Ngo

SUNY Campus: SUNY Buffalo

Presentation Type: Poster

Location: Old Union Hall

Presentation #: 30

Timeslot: Session C 1:45-2:45 PM

Abstract: Chronic inhalation of manganese (Mn) fumes by welders results in neurodegeneration of basal ganglia, causing Mangansim—a disorder similar to Parkinson’s disease but is distinct. The mechanism of neurotoxicity following chronic exposure to low-level exposure is unclear. However, progression of chronic inflammation without resolution results in increased reactive oxygen species and cell death. The failure to resolve neuroinflammation in microglial cells underlies the mechanism of Mn neurotoxicity. Hence, the objective is to study the differential gene expression of pro-inflammatory markers and mediators of the synthesis of leukotrienes. Microglia cells (HTHU) grown at 37 deg C/5 % CO2 were exposed to Mn fumes for 30 mins. The expression of inflammatory markers (IL6, IL10) and the mediators of the inflammation resolution (FPR2, BLT1, ALOX5, ALOX15) were evaluated after 24 hours in exposed cells and compared with Controls. To assess the differential expression of pro-inflammatory markers and mediators, cDNA synthesis was performed after total mRNA isolation. QPCR amplification of genes were performed using specific primers with SYBR and ROX as references. The quantification was performed using delta-delta Ct analysis. Within the Mn exposed microglial cells, the pro-inflammatory leukotrienes were differentially expressed compared to the mediators of the synthesis of the leukotrienes. ALOX5/15 and LTB4, a critical component of lipid metabolism/immune response, help resolve inflammation and promoting tissue healing. The identified differential expression of inflammation resolution markers needs to be validated with protein expression as it has great potential as a biomarker of an occupational hazard and a therapeutic target for neurodegeneration underlying Manganism.