Gene expression profiling of enhanced lung inflammation during pregnancy (134.54)

Abstract

Abstract Pregnant mice show sustained lung inflammation after exposure to environmental particles, titanium dioxide (TiO2), which are otherwise 'inert' in non-pregnant individuals (Am J Respir Cell Mol Biol. 2008. 38(1):57-67). We sought to characterize the gene expression program that underlies this inflammation by PCR array analysis. Selection of candidate genes for this array was informed by prior genome-wide chip microarray results, amended with hypothesis-driven candidates. METHODS: Pregnant E14 mice and controls received intranasal instillations of 50 ug/mouse of TiO2 particle suspensions or vehicle alone; n=5/group. After 48 hrs lungs were extracted, total lung RNA was isolated and samples were tested by real-time PCR via a custom 96-well PCR array (SABiosciences). Normalized dCt values were analyzed by pair-wise comparisons (ANOVA) and by main-effects tests (factorial ANOVA). RESULTS: Pregnant, but not control mice, show significant upregulation of ten genes (e.g. Itgax, CD4, Igsf6, Tlr2 and Tlr4) and a trend to upregulation of another ~20 genes, with fold change of 1.5-4.0. There is indication of influx of dendritic cells and T-helpers with some evidence of Th2 polarization. CONCLUSION: PCR array analysis identifies a gene expression signature for the enhanced inflammatory response to TiO2 particles seen in pregnant lungs, and suggests effects on adaptive immune responses. 1K99ES015425.