title: Ultrafine carbon particles induce interleukin-8 gene transcription and p38 MAPK activation in normal human bronchial epithelial cells.
abstract: Epidemiological studies suggest that ultrafine particles contribute to particulate matter-induced adverse health effects. Interleukin (IL)-8 is an important proinflammatory cytokine in the human lung that is induced in respiratory cells exposed to a variety of environmental insults, including ambient air ultrafine particles. In this study, we examined the effect of a model ultrafine particle on IL-8 expression and the cellular mechanisms responsible for this event. Here, we report that carbonaceous ultrafine particles consisting of synthetic elemental carbon particles (UfCP) markedly increase the expression of IL-8 mRNA and protein in normal human bronchial epithelial (NHBE) cells. IL-8 promoter activity was increased by UfCP exposure in NHBE cells, indicating UfCP-induced IL-8 expression is transcriptionally regulated. IL-8 expression in NHBE is known to be regulated by nuclear factor (NF)-kappaB activation. However, UfCP did not induce inhibitory factor kappaBalpha degradation, NF-kappaB-DNA binding, or NF-kappaB-dependent promoter activity in NHBE cells, indicating that UfCP induces IL-8 expression through a mechanism that is independent of NF-kappaB activation. Additionally, we observed that UfCP exposure induces the phosphorylation and activation of p38 mitogen-activated protein kinase (MAPK) in a biphasic manner and that the inhibition of p38 MAPK activity can block IL-8 mRNA expression induced by UfCP in NHBE cells. These results demonstrate that UfCP-induced expression of IL-8 involves a transcriptional mechanism and activation of p38 MAPK in NHBE cells.
authors.affiliation: Department of Environmental Sciences and Engineering, School of Public Health, University of North Carolina, Chapel Hill, North Carolina, USA.
authors.forename: Yu-Mee
authors.initials: YM
authors.lastname: Kim
authors.forename: William
authors.initials: W
authors.lastname: Reed
authors.forename: Anke G
authors.initials: AG
authors.lastname: Lenz
authors.forename: Ilona
authors.initials: I
authors.lastname: Jaspers
authors.forename: Robert
authors.initials: R
authors.lastname: Silbajoris
authors.forename: Harry S
authors.initials: HS
authors.lastname: Nick
authors.forename: James M
authors.initials: JM
authors.lastname: Samet
mesh_terms: D001980:Bronchi / Q000378:metabolism*; D002244:Carbon / Q000494:pharmacology*; D004789:Enzyme Activation; D004847:Epithelial Cells / Q000378:metabolism; D006801:Humans; D016209:Interleukin-8 / Q000235:genetics / Q000378:metabolism*; D016328:NF-kappa B / Q000378:metabolism; D010316:Particle Size; D010766:Phosphorylation / Q000187:drug effects; D011401:Promoter Regions, Genetic / Q000187:drug effects; D012333:RNA, Messenger / Q000378:metabolism; D014158:Transcription, Genetic; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism*
chemical_list: D016209:Interleukin-8; D016328:NF-kappa B; D012333:RNA, Messenger; D002244:Carbon; D048051:p38 Mitogen-Activated Protein Kinases