AMORPHOUS SILICA PARTICLES PROMOTE INFLAMMATORY GENE EXPRESSION THROUGH THE REDOX SENSITIVE TRANSCRIPTION FACTOR, AP-1, IN ALVEOLAR EPITHELIAL CELLS

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Abstract
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)-κB, 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 = κB inhibitor IκBc 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.