Background: Individuals with chronic lung disease are at increased risk of adverse health effects from airborne particulate matter. Characterization of underlying pollutant-phenotype interactions may require comprehensive strategies. Here, a toxicogenomic approach was used to investigate how inflammation modifies the pulmonary response to urban particulate matter.
Results: Transgenic mice with constitutive pulmonary overexpression of tumour necrosis factor (TNF)-alpha under the control of the surfactant protein C promoter and wildtype littermates (C57BL/6 background) were exposed by inhalation for 4 h to particulate matter (0 or 42 mg/m3 EHC-6802) and euthanized 0 or 24 h post-exposure. The low alveolar dose of particles (16 mug) did not provoke an inflammatory response in the lungs of wildtype mice, nor exacerbate the chronic inflammation in TNF animals. Real-time PCR confirmed particle-dependent increases of CYP1A1 (30-100%), endothelin-1 (20-40%), and metallothionein-II (20-40%) mRNA in wildtype and TNF mice (p < 0.05), validating delivery of a biologically-effective dose. Despite detection of striking genotype-related differences, including activation of immune and inflammatory pathways consistent with the TNF-induced pathology, and time-related effects attributable to stress from nose-only exposure, microarray analysis failed to identify effects of the inhaled particles. Remarkably, the presence of chronic inflammation did not measurably amplify the transcriptional response to particulate matter.
Conclusion: Our data support the hypothesis that health effects of acute exposure to urban particles are dominated by activation of specific physiological response cascades rather than widespread changes in gene expression.