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Title: Regulation of cytokine production in human alveolar macrophages and airway epithelial cells in response to ambient air pollution particles: Further mechanistic studies

Abstract

In order to better understand how ambient air particulate matter (PM) affect lung health, the two main airway cell types likely to interact with inhaled particles, alveolar macrophages (AM) and airway epithelial cells have been exposed to particles in vitro and followed for endpoints of inflammation, and oxidant stress. Separation of Chapel Hill PM 10 into fine and coarse size particles revealed that the main proinflammatory response (TNF, IL-6, COX-2) in AM was driven by material present in the coarse PM, containing 90-95% of the stimulatory material in PM10. The particles did not affect expression of hemoxygenase-1 (HO-1), a sensitive marker of oxidant stress. Primary cultures of normal human bronchial epithelial cells (NHBE) also responded to the coarse fraction with higher levels of IL-8 and COX-2, than induced by fine or ultrafine PM. All size PM induced oxidant stress in NHBE, while fine PM induced the highest levels of HO-1 expression. The production of cytokines in AM by both coarse and fine particles was blocked by the toll like receptor 4 (TLR4) antagonist E5531 involved in the recognition of LPS and Gram negative bacteria. The NHBE were found to recognize coarse and fine PM through TLR2, a receptor with preferencemore » for recognition of Gram positive bacteria. Compared to ambient PM, diesel PM induced only a minimal cytokine response in both AM and NHBE. Instead, diesel suppressed LPS-induced TNF and IL-8 release in AM. Both coarse and fine ambient air PM were also found to inhibit LPS-induced TNF release while silica, volcanic ash or carbon black had no inhibitory effect. Diesel particles did not affect cytokine mRNA induction nor protein accumulation but interfered with the release of cytokine from the cells. Ambient coarse and fine PM, on the other hand, inhibited both mRNA induction and protein production. Exposure to coarse and fine PM decreased the expression of TLR4 in the macrophages. Particle-induced decrease in TLR4 and hyporesponsiveness to LPS may be related to LPS tolerance induced by low levels of LPS.« less

Authors:
 [1];  [1];  [1];  [1]
  1. US Environmental Protection Agency, Human Studies Facility, National Health and Environmental Effects Research Laboratory, Research Triangle Park, 104 Mason Farm Road, Chapel Hill, NC 27599 (United States)
Publication Date:
OSTI Identifier:
20721920
Resource Type:
Journal Article
Journal Name:
Toxicology and Applied Pharmacology
Additional Journal Information:
Journal Volume: 207; Journal Issue: 2,suppl.1; Conference: ICT X 2004: 10. international congress of toxicology: Living in a safe chemical world, Tampere (Finland), 11-15 Jul 2004; Other Information: DOI: 10.1016/j.taap.2005.01.023; PII: S0041-008X(05)00230-9; Copyright (c) 2005 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved; Country of input: International Atomic Energy Agency (IAEA); Journal ID: ISSN 0041-008X
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; AIR POLLUTION; BACTERIA; BIOLOGICAL STRESS; CARBON BLACK; IN VITRO; INFLAMMATION; LUNGS; LYMPHOKINES; MACROPHAGES; OXIDIZERS; RECEPTORS

Citation Formats

Becker, Susanne, Mundandhara, Sailaja, Devlin, Robert B, and Madden, Michael. Regulation of cytokine production in human alveolar macrophages and airway epithelial cells in response to ambient air pollution particles: Further mechanistic studies. United States: N. p., 2005. Web. doi:10.1016/j.taap.2005.01.023.
Becker, Susanne, Mundandhara, Sailaja, Devlin, Robert B, & Madden, Michael. Regulation of cytokine production in human alveolar macrophages and airway epithelial cells in response to ambient air pollution particles: Further mechanistic studies. United States. https://doi.org/10.1016/j.taap.2005.01.023
Becker, Susanne, Mundandhara, Sailaja, Devlin, Robert B, and Madden, Michael. 2005. "Regulation of cytokine production in human alveolar macrophages and airway epithelial cells in response to ambient air pollution particles: Further mechanistic studies". United States. https://doi.org/10.1016/j.taap.2005.01.023.
@article{osti_20721920,
title = {Regulation of cytokine production in human alveolar macrophages and airway epithelial cells in response to ambient air pollution particles: Further mechanistic studies},
author = {Becker, Susanne and Mundandhara, Sailaja and Devlin, Robert B and Madden, Michael},
abstractNote = {In order to better understand how ambient air particulate matter (PM) affect lung health, the two main airway cell types likely to interact with inhaled particles, alveolar macrophages (AM) and airway epithelial cells have been exposed to particles in vitro and followed for endpoints of inflammation, and oxidant stress. Separation of Chapel Hill PM 10 into fine and coarse size particles revealed that the main proinflammatory response (TNF, IL-6, COX-2) in AM was driven by material present in the coarse PM, containing 90-95% of the stimulatory material in PM10. The particles did not affect expression of hemoxygenase-1 (HO-1), a sensitive marker of oxidant stress. Primary cultures of normal human bronchial epithelial cells (NHBE) also responded to the coarse fraction with higher levels of IL-8 and COX-2, than induced by fine or ultrafine PM. All size PM induced oxidant stress in NHBE, while fine PM induced the highest levels of HO-1 expression. The production of cytokines in AM by both coarse and fine particles was blocked by the toll like receptor 4 (TLR4) antagonist E5531 involved in the recognition of LPS and Gram negative bacteria. The NHBE were found to recognize coarse and fine PM through TLR2, a receptor with preference for recognition of Gram positive bacteria. Compared to ambient PM, diesel PM induced only a minimal cytokine response in both AM and NHBE. Instead, diesel suppressed LPS-induced TNF and IL-8 release in AM. Both coarse and fine ambient air PM were also found to inhibit LPS-induced TNF release while silica, volcanic ash or carbon black had no inhibitory effect. Diesel particles did not affect cytokine mRNA induction nor protein accumulation but interfered with the release of cytokine from the cells. Ambient coarse and fine PM, on the other hand, inhibited both mRNA induction and protein production. Exposure to coarse and fine PM decreased the expression of TLR4 in the macrophages. Particle-induced decrease in TLR4 and hyporesponsiveness to LPS may be related to LPS tolerance induced by low levels of LPS.},
doi = {10.1016/j.taap.2005.01.023},
url = {https://www.osti.gov/biblio/20721920}, journal = {Toxicology and Applied Pharmacology},
issn = {0041-008X},
number = 2,suppl.1,
volume = 207,
place = {United States},
year = {Thu Sep 01 00:00:00 EDT 2005},
month = {Thu Sep 01 00:00:00 EDT 2005}
}