Chronic Inhaled LPS Exposure

Chronic LPS inhalation causes submucosal thickening and airway narrowing. To address the hypothesis that environmental airway disease is, in part, a fibroproliferative lung disease, we exposed C57BL/6 mice daily to LPS by inhalation for up to two months followed by one month of recovery. C57BL/6 mice exposed to daily inhaled LPS had significantly enhanced mRNA expression of TGF-beta1, TIMP-1, fibronectin-1, and pro-collagen types I, III, and IV and show prominent submucosal expression of the myofibroblast markers desmin and alpha-smooth muscle actin. To identify novel candidate genes that contribute to airway fibroproliferation, we performed microarray analysis on total lung RNA from mice exposed to LPS for one week. This analysis revealed a distinct subset of genes known to regulate ECM homeostasis. To further identify candidate genes specifically involved in generic fibroproliferation we interrogated this analysis with genes induced in C57BL/6 mouse lung by bleomycin. This analysis yielded a list of 212 genes in common. Prominent among which are genes know to be important in maintenance of bone homeostasis and which may play a central role in ECM homeostasis in the lung. These results suggest that there is a common subset of genes that regulate fibroproliferation in the lung independent of etiologic agent and site of injury. Keywords: mouse model of environmental airway disease; chronic LPS exposure 4 RNA pools of 3 animals each exposed to aerosolized LPS and 4 RNA pools of 3 animals each exposed to air only were co-hybridized with the Stratagene Universal Mouse Reference RNA. Each sample was assayed in duplicate with Cy3 and Cy5 dyes swapped.