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Roles of reactive oxygen species, HEME oxygenase-1, and nitric oxide in diesel exhaust particle-mediated pulmonary immune responses to listeria monocytogenes in rats.

Authors
Yin-X; Ma-J; Antonini-J; Ma-J
Source
Toxicologist 2003 Mar; 72(S-1):375
NIOSHTIC No.
20022701
Abstract
This study examines the hypothesis that diesel exhaust particles (DEP) suppress pulmonary immunity to Listeria monocytogenes (Listeria) through the induction of reactive oxygen species (ROS), heme oxygenase-1 (HO-1) and altered cytokine production by alveolar macrophages (AM) and lymphocytes. Cells were isolated from Brown Norway rats intratracheally inoculated with saline or 100,000 Listeria at 7 days post-infection. The Listeria-infected AM showed increased production of IL-6, IL-10, IL-12, and TNF-alpha over the saline control in response to lipopolysacchride (LPS), whereas the Listeria-infected lymphocytes showed increased production of IL-2, IL-10, and IFN-gamma when challenged with concanavalin A (ConA) or heat killed Listeria (HKLM). DEP or DEP extract, but not the washed DEP, inhibited AM secretion of IL-6, IL-12, and TNF-alpha and lymphocyte production of IL-2 and IFN-gamma, but enhanced AM production of IL-10. The effect of the DEP extract on cytokine production was preceded by a time-dependent induction of ROS and ROS-induced HO-1 protein and activity in AM. alpha-Naphthoflavone (ANF), a CYP 1A1 inhibitor, partially inhibited DEP-induced ROS and HO-1 expression and reversed the DEP effect on cytokine secretion. L-NAME (N-nitro-L-arginine methyl ester), a NO synthase inhibitor, inhibited the DEP-induced ROS generation and HO-1 induction, but augmented the DEP-induced IL-10 production by Listeria-infected AM, suggesting that NO down-regulates IL-10 production. Similar to DEP extract, hemin induced HO-1 expression, an increase in IL-10 and a decrease in TNF-alpha production by AM. In comparison, DEP extract at a level that induced less HO-1 than hemin, showed greater effect on IL-10 secretion. These results show that both HO-1 and NO play a role in AM production of IL-10, and that due to its organic content, DEP suppress the host immune responses by inhibiting the innate and T cell-mediated immunity and augmenting AM production of IL-10 (NIH HL-62630).
Keywords
Diesel-exhausts; Particulate-dust; Particulates; Dusts; Pulmonary-system; Lymphocytes; Laboratory-animals; Animal-studies; Animals; Combustion-gases; Combustion-products
Publication Date
20030301
Document Type
Abstract
Fiscal Year
2003
NTIS Accession No.
NTIS Price
ISSN
1096-6080
NIOSH Division
HELD
Priority Area
Work Environment and Workforce: Mixed Exposures
Source Name
The Toxicologist. Society of Toxicology 42nd Annual Meeting and ToxExpo, Cutting-Edge Science, Networking, New Perspectives, March 9-13, 2003, Salt Lake City, Utah
State
WV
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