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Taiyuan is a center of coal-based electricity production and many chemicals industries, where mixtures of sulfur dioxide (SO2) and particulate matter may be more prominent. The focus of the present study was to determine if there is a link between adverse effects in the brain and the combined-exposure to SO2and fine particulate matter (PM2.5). Rats were exposed alternately to PM2.5with different dosages (1.5, 6.0 and 24.0 mg/kg body weight) and SO2at the level of 5.6 mg/m3. The results showed that the combined exposure to PM2.5and SO2enhanced the mRNA expression and protein level of TNF-α and IL-6 in rat cortex and hippocampus relative to the control, SO2and PM2.5alone. Instead, TGF-β1 mRNA and protein level were down-regulated in the brain. Additionally, PM2.5at medium and/or high dose caused marked increase in Aβ42 level and PM2.5 + SO2induced further increase of Aβ42 level in the cortex and hippocampus. It suggests that SO2and PM2.5can synergistically exert inflammation responses and induce Aβ42 accumulation in the brain. Also, it is notable that the Aβ42 accumulation of rat cortex and hippocampus were closely associated with pro-/anti-inflammatory cytokines ratio. These results clearly demonstrated that the combined exposure to PM2.5and SO2can induce the imbalance of pro-/anti-inflammatory cytokine, resulting in Aβ42 accumulation of rat brain cortex and hippocampus. [ABSTRACT FROM AUTHOR]