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.

In-vitro cell exposure studies for the assessment of nanoparticle toxicity in the lung—A dialog between aerosol science and biology

“…These studies have typically been performed under submerged culture conditions, where the agent to be investigated (here: nanoparticles) is added to the culture medium, which completely covers the cells grown on the bottom of the cell culture dish (Maier et al, 2008;Kim et al, 2005). With this approach a wide variety of biological endpoints and nanoparticles have been investigated including ambient and occupational particles (e.g.…”

Barrier responses of human bronchial epithelial cells to grass pollen exposure

“…We found that ERK1/2 and p38 MAPK signalling pathways were involved in the apical, but not in basolateral, release of CXCL8/ IL-8. Involvement of ERK1/2 and p38 MAPK pathways in CXCL8/IL-8 release has been previously shown by others using different challenges [35,36], but in all these studies cell-line models or undifferentiated PBECs were used. In our analysis, we found that p38 activation and CXCL8/IL-8 mRNA expression occurred rapidly after pollen exposure; however inhibition of p38 MAPK did not affect CXCL8/IL-8 mRNA levels.…”

The impact of air pollutants as an adjuvant for allergic sensitization and asthma

“…These cytokines/chemokines promote recruitment and local survival of immature DCs. DEP induction of cytokine/chemokine release proceeds, in part, through the activation of the MAPK pathways, specifi cally the ERK 1 and 2 pathways and the p38 pathway, which have been demonstrated to be involved in DEP-induced secretion of MIP 3 α , GM-CSF, IL-8, and amphiregulin from epithelial cells [28][29][30][31].…”