PM(10)-exposed macrophages stimulate a proinflammatory response in lung epithelial cells via TNF-alpha

There is now considerable evidence for an association between the levels of particulate air pollution [particulate matter <10 microm in aerodynamic diameter (PM(10))] and various adverse health endpoints. The release of proinflammatory mediators from PM(10)-exposed macrophages may be important in stimulating cytokine release from lung epithelial cells, thus amplifying the inflammatory response. A549 cells were treated with conditioned media from monocyte-derived macrophages stimulated with PM(10), titanium dioxide (TiO(2)), or ultrafine TiO(2). We demonstrate that only conditioned media from PM(10)-stimulated macrophages significantly increased nuclear factor-kappaB and activator protein-1 DNA binding, enhanced interleukin-8 (IL-8) mRNA levels as assessed by RT-PCR, and augmented IL-8 protein levels, over untreated controls. Furthermore, PM(10)-conditioned media also caused transactivation of IL-8 as determined by an IL-8-chloramphenicol acetyl transferase reporter. Analysis of these conditioned media revealed marked increases in tumor necrosis factor-alpha (TNF-alpha) and protein levels and enhanced chemotactic activity for neutrophils. Preincubation of conditioned media with TNF-alpha-neutralizing antibodies significantly reduced IL-8 production. These data suggest that PM(10)-activated macrophages may amplify the inflammatory response by enhancing IL-8 release from lung epithelial cells, in part, via elaboration of TNF-alpha.