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ULTRAFINE CARBON PARTICLES INDUCE INTERLEUKIN-8 GENE TRANSCRIPTION AND P38 MAPK ACTIVATION IN NORMAL BRONCHIAL EPITHELIAL CELLS
Citation:
KIM, C. S., W. REED, A. LENZ, I. JASPERS, R. A. SILBAJORIS, H. S. NICK, AND J. M. SAMET. ULTRAFINE CARBON PARTICLES INDUCE INTERLEUKIN-8 GENE TRANSCRIPTION AND P38 MAPK ACTIVATION IN NORMAL BRONCHIAL EPITHELIAL CELLS. American Journal of Physiology - Lung Cellular and Molecular Physiology. American Physiological Society, Bethesda, MD, 288(3):432-441, (2005).
Impact/Purpose:
To examine the effect of a model ultrafine particle on Interleukin-8 expression and the cellular mechanisms responsible for this event
Description:
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