Exposure to ambient PM 2.5 is associated with neurodegenerative disorders, in which microglia activation plays a critical role. Thus far, the underlying mechanisms for PM 2.5 -induced microglia activation have not been well elucidated. In this study, a human microglial cell line (HMC3) was used as the in vitro model to examine the inflammatory effect (hall marker of microglia activation) of PM 2.5 and regulatory pathways. The expression of inflammatory mediators including interleukin-6 (IL-6) and cyclooxygenase-2 (COX-2) as well as the brain derived neurotrophic factor (BDNF) were determined by ELISA and/or real-time PCR, respectively. Flow cytometry was used to measure the production of intracellular reactive oxygen species (ROS). Western blot was used to measure protein levels of Toll-like receptor 4 (TLR4), NF-κB inhibitor α (IκBα) and COX-2. It was shown that PM 2.5 stimulation increased IL-6 and COX-2 expression but decreased BDNF expression in a dose-dependent manner. Further studies showed that PM 2.5 triggered the formation of ROS and pre-treatment with the ROS scavenger acetylcysteine (NAC) significantly suppressed PM 2.5 -induced IL-6 and COX-2 expression. Moreover, the nuclear factor kappa B (NF-κB) inhibitor BAY11–7085 or the TLR4 neutralizing antibody markedly blocked PM 2.5 -induced IL-6 and COX-2 expression. However, NAC or BAY11–7085 exhibited minimal effect on PM 2.5 -induced BDNF down-regulation. In addition, pre-treatment with BAY11–7085 or TLR4 neutralizing antibody reduced ROS production induced by PM 2.5 , and NAC pre-treatment inhibited TLR4 expression and NF-κB activation induced by PM 2.5 . Collectively, PM 2.5 treatment induced IL-6 and COX-2 but suppressed BDNF expression. PM 2.5 -induced IL-6 and COX-2 expression was mediated by interactive oxidative stress and TLR4/NF-κB pathway.
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Human IL-6 High Sensitivity ELISA Kit检测试剂盒(酶联免疫吸附法)
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