Amorphous silica particles promote inflammatory gene expression through the redox sensitive transcription factor, AP-1, in alveolar epithelial cells.
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.
Singal
Madhuri
M
Department of Environmental Medicine, School of Medicine and Dentistry, The University of Rochester, New York 14642, USA.
Finkelstein
Jacob N
JN
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D002083:Butylated Hydroxyanisole / Q000494:pharmacology; D002460:Cell Line; D054426:Chemokine CXCL2; D018925:Chemokines / Q000235:genetics; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004847:Epithelial Cells / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects / Q000276:immunology; D006419:Heme Oxygenase (Decyclizing) / Q000378:metabolism; D051547:Heme Oxygenase-1; D020672:I-kappa B Proteins / Q000378:metabolism; D020935:MAP Kinase Signaling System / Q000187:drug effects; D009115:Muridae; D000072000:NF-KappaB Inhibitor alpha; D010084:Oxidation-Reduction; D011014:Pneumonia / Q000139:chemically induced / Q000276:immunology / Q000503:physiopathology*; D011650:Pulmonary Alveoli / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D020545:Respiratory Mucosa / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D012822:Silicon Dioxide / Q000494:pharmacology*; D018808:Transcription Factor AP-1 / Q000378:metabolism*
D000975:Antioxidants; D054426:Chemokine CXCL2; D018925:Chemokines; C404915:Cxcl2 protein, mouse; D004791:Enzyme Inhibitors; D020672:I-kappa B Proteins; C000606205:Nfkbia protein, mouse; D018808:Transcription Factor AP-1; D000072000:NF-KappaB Inhibitor alpha; D002083:Butylated Hydroxyanisole; D012822:Silicon Dioxide; D006419:Heme Oxygenase (Decyclizing); D051547:Heme Oxygenase-1