Singal Madhuri, Finkelstein Jacob N
Department of Environmental Medicine, School of Medicine and Dentistry, The University of Rochester, New York 14642, USA.
Exp Lung Res. 2005 Jul-Aug;31(6):581-97. doi: 10.1080/019021490951504.
Ultrafine particulate (UFP) matter, from environmental or industrial exposure, can induce expression of inflammatory mediators and promote production of reactive oxygen species. Previous studies showed various cellular stresses activate signaling pathways operating through specific transcription factors (TFs), activator protein (AP)-1 and nuclear factor (NF)-kappaB, known to regulate inflammatory gene expression. Exposing MLE15 cells to inflammatory, or UFP, stimuli increased macrophage inflammatory protein (MIP)-2 protein, in the absence of the NF = kappaB inhibitor IkappaBc degradation, synergistically increasing in the presence of proteosomal inhibition. Although thiol antioxidants attenuate MIP-2 induction, mitogen-activated protein kinase (MAPK) inhibitors significantly inhibit MIP-2 protein production. This suggests UFP promote inflammatory gene expression through the redox responsive TF AP-1.
环境或工业暴露产生的超细颗粒物（UFP）可诱导炎症介质的表达并促进活性氧的产生。先前的研究表明，各种细胞应激会激活通过特定转录因子（TFs）、激活蛋白（AP）-1和核因子（NF）-κB起作用的信号通路，已知这些因子可调节炎症基因的表达。在不存在NF-κB抑制剂IkappaBc降解的情况下，将MLE15细胞暴露于炎症或UFP刺激下会增加巨噬细胞炎性蛋白（MIP）-2蛋白的表达，在蛋白酶体抑制存在的情况下会协同增加。尽管硫醇抗氧化剂可减弱MIP-2的诱导，但丝裂原活化蛋白激酶（MAPK）抑制剂可显著抑制MIP-2蛋白的产生。这表明UFP通过氧化还原反应性TF AP-1促进炎症基因的表达。
