Contribution of IL-1 and TNF- to the initiation of the peripheral lung response to atmospheric particulates (PM10)

Ishii, Hiroshi, Takeshi Fujii, James C. Hogg, Shizu Hayashi, Hiroshi Mukae, Renaud Vincent, and Stephan F. van Eeden. Contribution of IL-1 and TNFto the initiation of the peripheral lung response to atmospheric particulates (PM10). Am J Physiol Lung Cell Mol Physiol 287: L176–L183, 2004. First published March 5, 2004; 10.1152/ajplung.00290.2003.—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 TNFand IL-1 released by AM exposed to ambient particulate matter with a diameter of 10 m (PM10) 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 PM10 (100 g/ml) contained more TNF, IL-1 , granulocyte-macrophage colony stimulating factor, IL-6, and IL-8 than nonexposed AM supernatants. The 3-h treatment of A549 cells with PM10-exposed AM supernatants increased TNF, 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 PM10-exposed AM supernatants with anti-IL-1 antibodies reduced all the above mediators as well as VEGF mRNA expression (P 0.05), while anti-TNFantibodies were less effective (P 0.05), and the combination of the two antibodies most effective. When HBEC were treated similarly, anti-TNFantibodies had the greatest effect. In A549 cells PM10-exposed AM supernatants increased NFB, activator protein (AP)-1 and specificity protein 1 binding, while anti-TNFand anti-IL-1 antibodies reduced NFB and AP-1 binding. We conclude that AM-derived TNFand 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.