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.
Jiménez
L A
LA
Edinburgh Lung and the Environment Group Initiative/Colt Laboratories, Department of Medical and Radiological Sciences, University of Edinburgh, Edinburgh EH8 9AG, Scotland, United Kingdom. ajimenez@srv1.med.ed.ac.uk
Drost
E M
EM
Gilmour
P S
PS
Rahman
I
I
Antonicelli
F
F
Ritchie
H
H
MacNee
W
W
Donaldson
K
K
D000393:Air Pollutants / Q000494:pharmacology*; D000906:Antibodies / Q000494:pharmacology; D002460:Cell Line; D002634:Chemotaxis, Leukocyte / Q000187:drug effects / Q000276:immunology; D017077:Culture Media, Conditioned / Q000494:pharmacology; D004268:DNA-Binding Proteins / Q000378:metabolism; D004847:Epithelial Cells / Q000166:cytology / Q000276:immunology*; D015870:Gene Expression / Q000187:drug effects / Q000276:immunology; D006801:Humans; D007375:Interleukin-1 / Q000378:metabolism; D016209:Interleukin-8 / Q000235:genetics; D016676:Macrophages, Alveolar / Q000187:drug effects / Q000276:immunology*; D016328:NF-kappa B / Q000378:metabolism; D009504:Neutrophils / Q000166:cytology; D010316:Particle Size; D011401:Promoter Regions, Genetic / Q000502:physiology; D011650:Pulmonary Alveoli / Q000166:cytology / Q000276:immunology*; D012333:RNA, Messenger / Q000032:analysis; D018808:Transcription Factor AP-1 / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology / Q000378:metabolism*
D000393:Air Pollutants; D000906:Antibodies; D017077:Culture Media, Conditioned; D004268:DNA-Binding Proteins; D007375:Interleukin-1; D016209:Interleukin-8; D016328:NF-kappa B; D012333:RNA, Messenger; D018808:Transcription Factor AP-1; D014409:Tumor Necrosis Factor-alpha