Pulmonary Gene Expression Profiling of Inhaled Ricin
ARMY MEDICAL RESEARCH INST OF INFECTIOUS DISEASES FORT DETRICK MD DIV OF TOXINOLOGY AND AEROBIOLOGY
Pagination or Media Count:
Aerosol exposure to ricin causes irreversible pathological changes of the respiratory tract resulting in epithelial necrosis, pulmonary edema and ultimately death. The pulmonary genomic profile of BALBc mice inhalationally exposed to a lethal dose of ricin was examined using cDNA arrays. The expression profile of 1178 mRNA species was determined for ricin-exposed lung tissue, in which 34 genes had statistically significant changes in gene expression. Transcripts identified by the assay included those that facilitate tissue healing early growth response gene egr-1, regulate inflammation interleukin IL-6, tristetraproline ttp, cell growth c-myc, cytokine-inducible SH2-containing protein cish- 3, apoptosis T-cell death associated protein tdag51, pim-1 and DNA repair ephrin type A receptor 2 ephA2. Manipulation of these gene products may provide a means of limiting the severe lung damage occurring at the cellular level. Transcriptional activation of egr-1, cish-3, c-myc and thrombospondin tsp-1 was already apparent when pathological and physiological changes were observed in the lungs at 12 h postexposure. These genes may well serve as markers for ricin-induced pulmonary toxicity. Ongoing studies are evaluating this aspect of the array data and the potential of several genes for clinical intervention.
- Genetic Engineering and Molecular Biology