Diesel exhaust particles override natural injury-limiting pathways in the lung

N. Chaudhuri, C. Paiva, K. Donaldson, R. Duffin, L. C. Parker, I. Sabroe

Research output: Contribution to journalArticlepeer-review

Abstract

Chaudhuri N, Paiva C, Donaldson K, Duffin R, Parker LC, Sabroe I. Diesel exhaust particles override natural injury-limiting pathways in the lung. Am J Physiol Lung Cell Mol Physiol 299: L263-L271, 2010. First published April 30, 2010; doi:10.1152/ajplung.00297.2009.-Induction of effective inflammation in the lung in response to environmental and microbial stimuli is dependent on cooperative signaling between leukocytes and lung tissue cells. We explored how these inflammatory networks are modulated by diesel exhaust particles (DEP) using cocultures of human monocytes with epithelial cells. Cocultures, or monoculture controls, were treated with DEP in the presence or absence of LPS or flagellin. Production of cytokines was explored by Western blotting and ELISA; cell signaling was analyzed by Western blotting. Here, we show that responses of epithelial cells to DEP are amplified by the presence of monocytes. DEP amplified the responses of cellular cocultures to very low doses of TLR agonists. In addition, in the presence of DEP, the responses induced by LPS or flagellin were less amenable to antagonism by the physiological IL-1 antagonist, IL-1ra. This was paralleled by the uncoupling of IL-1 production and release from monocytes, potentially attributable to an ability of DEP to sequester or degrade extracellular ATP. These data describe a model of inflammation where DEP amplifies responses to low concentrations of microbial agonists and alters the nature of the inflammatory milieu induced by TLR agonists.

Original languageEnglish
Pages (from-to)L263-L271
Number of pages9
JournalAmerican Journal of Physiology - Lung Cellular and Molecular Physiology
Volume299
Issue number2
DOIs
Publication statusPublished - Aug 2010

Fingerprint

Dive into the research topics of 'Diesel exhaust particles override natural injury-limiting pathways in the lung'. Together they form a unique fingerprint.

Cite this