Postnatal Lung Development: Immediate-Early Gene Responses Post Ozone and LPS Exposure
Exposure to environmental pollutants may severely affect lung growth and development. The present study was designed to test the hypothesis that lung damage caused either by ozone or lipopolysaccharide (LPS) occurs through distinct early responses, which are age dependent in the postnatal lung. C57B...
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Veröffentlicht in: | Inhalation toxicology 2006-10, Vol.18 (11), p.875-883 |
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Zusammenfassung: | Exposure to environmental pollutants may severely affect lung growth and development. The present study was designed to test the hypothesis that lung damage caused either by ozone or lipopolysaccharide (LPS) occurs through distinct early responses, which are age dependent in the postnatal lung. C57Bl/6 mice ages 4, 10, and 56 days were exposed to inhalation of LPS with an estimated deposited dose of 26 EU and examined 0.5, 1, or 4 h post inhalation exposure; or to 1 or 2.5 ppm ozone for 4 h or sequential exposures of LPS followed by ozone. Abundance of c-fos, c-jun, interleukin (IL)-1β, Toll-like receptor (TLR) 2, TLR 4, and tumor necrosis factor (TNF) α message levels were measured by RNase protection assay. Exposure to ozone for 4 h induced a c-fos and c-jun response in 4-; 10-; and 56-day-old mice in a dose-dependent manner, was localized to conducting and terminal airways, and also induced TLR 4 message abundance in 10- and 56-day-old mice. Exposure to LPS induced c-fos and c-jun 30 and 60 min postinhalation in 10- and 56-day-old mice only. TLR 2 and 4 message abundance was increased at 10 and 56 days, but was undetectable at 4 days of age, and correlated with proinflamatory message induction. Exposure to LPS followed by ozone increased message abundance of IL-1β, TNFα, TLR 2, TLR 4, and c-jun/c-fos at 10 and 56 days, suggesting that combined exposures that induce cellular stresses can regulate gene expression by activating signaling pathways that operate through both transcription factors activator protein (AP)-1 and nuclear factor (NF)-κB. However, only c-jun/c-fos and TNFα were elevated in 4-day-old mice after sequential exposures, suggesting that the early activation of the inflammatory response after sequential exposures may occur through a TLR-independent pathway. These results suggest that sequential exposures induce multiple signaling pathways that are age dependent. |
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ISSN: | 0895-8378 1091-7691 |
DOI: | 10.1080/08958370600822466 |