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Contribution of IL-1β and TNF-α to the initiation of the peripheral lung response to atmospheric particulates (PM 10 )

Contribution of IL-1β and TNF-α to the initiation of the peripheral lung response to atmospheric... Alveolar macrophages (AM) play a key role in clearing atmospheric particulates from the lung surface and stimulating epithelial cells to produce proinflammatory mediators. The present study examines the role of "acute response" cytokines TNF-α and IL-1 released by AM exposed to ambient particulate matter with a diameter of <10 µm (PM 10 ) in amplifying the proinflammatory mediator expression by A549 cells and human bronchial epithelial cells (HBEC). The results showed that supernatants from human AM incubated 24 h with PM 10 (100 µg/ml) contained more TNF-α, IL-1 , granulocyte-macrophage colony stimulating factor, IL-6, and IL-8 than nonexposed AM supernatants. The 3-h treatment of A549 cells with PM 10 -exposed AM supernatants increased TNF-α, IL-1 , IL-8, regulated on activation normal T-cells expressed and secreted (RANTES), and leukemia inhibitory factor mRNA compared with the treatment with nonexposed AM supernatants and, compared with untreated A549 cells, additionally increased ICAM-1 and monocyte chemotactic protein-1 mRNA. Preincubating PM 10 -exposed AM supernatants with anti-IL-1 antibodies reduced all the above mediators as well as VEGF mRNA expression ( P < 0.05), while anti-TNF-α antibodies were less effective ( P > 0.05), and the combination of the two antibodies most effective. When HBEC were treated similarly, anti-TNF-α antibodies had the greatest effect. In A549 cells PM 10 -exposed AM supernatants increased NF-κB, activator protein (AP)-1 and specificity protein 1 binding, while anti-TNF-α and anti-IL-1 antibodies reduced NF-κB and AP-1 binding. We conclude that AM-derived TNF-α and IL-1 provide a major stimulus for the production of proinflammatory mediators by lung epithelial cells and that their relative importance may depend on the type of epithelial cell target. ribonuclease protection assay; transcription factors; enzyme-linked immunosorbent assay; proinflammatory mediators; particulate matter with diameter < 10 µm Address for reprint requests and other correspondence: S. F. van Eeden, iCAPTURE Centre, St. Paul's Hospital, Univ. of British Columbia, 1081 Burrard St., Vancouver, BC, Canada V6Z 1Y6 (E-mail: [email protected] ). http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png AJP - Lung Cellular and Molecular Physiology The American Physiological Society

Contribution of IL-1β and TNF-α to the initiation of the peripheral lung response to atmospheric particulates (PM 10 )

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Publisher
The American Physiological Society
Copyright
Copyright © 2011 the American Physiological Society
ISSN
1040-0605
eISSN
1522-1504
DOI
10.1152/ajplung.00290.2003
pmid
15003925
Publisher site
See Article on Publisher Site

Abstract

Alveolar macrophages (AM) play a key role in clearing atmospheric particulates from the lung surface and stimulating epithelial cells to produce proinflammatory mediators. The present study examines the role of "acute response" cytokines TNF-α and IL-1 released by AM exposed to ambient particulate matter with a diameter of <10 µm (PM 10 ) in amplifying the proinflammatory mediator expression by A549 cells and human bronchial epithelial cells (HBEC). The results showed that supernatants from human AM incubated 24 h with PM 10 (100 µg/ml) contained more TNF-α, IL-1 , granulocyte-macrophage colony stimulating factor, IL-6, and IL-8 than nonexposed AM supernatants. The 3-h treatment of A549 cells with PM 10 -exposed AM supernatants increased TNF-α, IL-1 , IL-8, regulated on activation normal T-cells expressed and secreted (RANTES), and leukemia inhibitory factor mRNA compared with the treatment with nonexposed AM supernatants and, compared with untreated A549 cells, additionally increased ICAM-1 and monocyte chemotactic protein-1 mRNA. Preincubating PM 10 -exposed AM supernatants with anti-IL-1 antibodies reduced all the above mediators as well as VEGF mRNA expression ( P < 0.05), while anti-TNF-α antibodies were less effective ( P > 0.05), and the combination of the two antibodies most effective. When HBEC were treated similarly, anti-TNF-α antibodies had the greatest effect. In A549 cells PM 10 -exposed AM supernatants increased NF-κB, activator protein (AP)-1 and specificity protein 1 binding, while anti-TNF-α and anti-IL-1 antibodies reduced NF-κB and AP-1 binding. We conclude that AM-derived TNF-α and IL-1 provide a major stimulus for the production of proinflammatory mediators by lung epithelial cells and that their relative importance may depend on the type of epithelial cell target. ribonuclease protection assay; transcription factors; enzyme-linked immunosorbent assay; proinflammatory mediators; particulate matter with diameter < 10 µm Address for reprint requests and other correspondence: S. F. van Eeden, iCAPTURE Centre, St. Paul's Hospital, Univ. of British Columbia, 1081 Burrard St., Vancouver, BC, Canada V6Z 1Y6 (E-mail: [email protected] ).

Journal

AJP - Lung Cellular and Molecular Physiology – The American Physiological Society

Published: Jul 1, 2004

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