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

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-1β released by AM exposed to ambient particulate matter with a diameter of <10 μm (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 μg/ml) contained more TNF-α, IL-1β, 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-α, IL-1β, 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-1β 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 PM10-exposed AM supernatants increased NF-κB, activator protein (AP)-1 and specificity protein 1 binding, while anti-TNF-α and anti-IL-1β antibodies reduced NF-κB and AP-1 binding. We conclude that AM-derived TNF-α and IL-1β 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.