Browsing by Author "Dailey, Lisa A"

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Open Access
Pollutant particles produce vasoconstriction and enhance MAPK signaling via angiotensin type I receptor.
(Environmental health perspectives, 2005-08) Li, Zhuowei; Carter, Jacqueline D; Dailey, Lisa A; Huang, Yuh-Chin T
Exposure to particulate matter (PM) is associated with acute cardiovascular mortality and morbidity, but the mechanisms are not entirely clear. In this study, we hypothesized that PM may activate the angiotensin type 1 receptor (AT1R), a G protein-coupled receptor that regulates inflammation and vascular function. We investigated the acute effects of St. Louis, Missouri, urban particles (UPs; Standard Reference Material 1648) on the constriction of isolated rat pulmonary artery rings and the activation of extracellular signal-regulated kinases 1 and 2 (ERK1/2) and p38 mitogen-activated protein kinases (MAPKs) in human pulmonary artery endothelial cells with or without losartan, an antagonist of AT1R. UPs at 1-100 microg/mL induced acute vasoconstriction in pulmonary artery. UPs also produced a time- and dose-dependent increase in phosphorylation of ERK1/2 and p38 MAPK. Losartan pretreatment inhibited both the vasoconstriction and the activation of ERK1/2 and p38. The water-soluble fraction of UPs was sufficient for inducing ERK1/2 and p38 phosphorylation, which was also losartan inhibitable. Copper and vanadium, two soluble transition metals contained in UPs, induced pulmonary vasoconstriction and phosphorylation of ERK1/2 and p38, but only the phosphorylation of p38 was inhibited by losartan. The UP-induced activation of ERK1/2 and p38 was attenuated by captopril, an angiotensin-converting enzyme inhibitor. These results indicate that activation of the local renin-angiotensin system may play an important role in cardiovascular effects induced by PM.
Open Access
Seasonal variations in air pollution particle-induced inflammatory mediator release and oxidative stress.
(Environmental health perspectives, 2005-08) Becker, Susanne; Dailey, Lisa A; Soukup, Joleen M; Grambow, Steven C; Devlin, Robert B; Huang, Yuh-Chin T
Health effects associated with particulate matter (PM) show seasonal variations. We hypothesized that these heterogeneous effects may be attributed partly to the differences in the elemental composition of PM. Normal human bronchial epithelial (NHBE) cells and alveolar macrophages (AMs) were exposed to equal mass of coarse [PM with aerodynamic diameter of 2.5-10 microm (PM(2.5-10)], fine (PM(2.5)), and ultrafine (PM(<0.1)) ambient PM from Chapel Hill, North Carolina, during October 2001 (fall) and January (winter), April (spring), and July (summer) 2002. Production of interleukin (IL)-8, IL-6, and reactive oxygen species (ROS) was measured. Coarse PM was more potent in inducing cytokines, but not ROSs, than was fine or ultrafine PM. In AMs, the October coarse PM was the most potent stimulator for IL-6 release, whereas the July PM consistently stimulated the highest ROS production measured by dichlorofluorescein acetate and dihydrorhodamine 123 (DHR). In NHBE cells, the January and the October PM were consistently the strongest stimulators for IL-8 and ROS, respectively. The July PM increased only ROS measured by DHR. PM had minimal effects on chemiluminescence. Principal-component analysis on elemental constituents of PM of all size fractions identified two factors, Cr/Al/Si/Ti/Fe/Cu and Zn/As/V/Ni/Pb/Se, with only the first factor correlating with IL-6/IL-8 release. Among the elements in the first factor, Fe and Si correlated with IL-6 release, whereas Cr correlated with IL-8 release. These positive correlations were confirmed in additional experiments with PM from all 12 months. These results indicate that elemental constituents of PM may in part account for the seasonal variations in PM-induced adverse health effects related to lung inflammation.
Open Access
Vanadyl sulfate inhibits NO production via threonine phosphorylation of eNOS.
(Environmental health perspectives, 2004-02) Li, Zhuowei; Carter, Jacqueline D; Dailey, Lisa A; Huang, Yuh-Chin T
Exposure to excessive vanadium occurs in some occupations and with consumption of some dietary regimens for weight reduction and body building. Because vanadium is vasoactive, individuals exposed to excessive vanadium may develop adverse vascular effects. We have previously shown that vanadyl sulfate causes acute pulmonary vasoconstriction, which could be attributed in part to inhibition of nitric oxide production. In the present study we investigated whether NO inhibition was related to phosphorylation of endothelial nitric oxide synthase (eNOS). VOSO4 produced dose-dependent constriction of pulmonary arteries in isolated perfused lungs and pulmonary arterial rings and a right shift of the acetylcholine-dependent vasorelaxation curve. VOSO4 inhibited constitutive as well as A23187-stimulated NO production. Constitutive NO inhibition was accompanied by increased Thr495 (threonine at codon 495) phosphorylation of eNOS, which would inhibit eNOS activity. Thr495 phosphorylation of eNOS and inhibition of NO were partially reversed by pretreatment with calphostin C, a protein kinase C (PKC) inhibitor. There were no changes in Ser1177 (serine at codon 1177) or tyrosine phosphorylation of eNOS. These results indicate that VOSO4 induced acute pulmonary vasoconstriction that was mediated in part by the inhibition of endothelial NO production via PKC-dependent phosphorylation of Thr495 of eNOS. Exposure to excessive vanadium may contribute to pulmonary vascular diseases.