Inhibition of LPS-induced acute lung inflammation in mice by adenovirus mediated Foxp3 expression (HYP6P.275)

Abstract

Abstract Forkhead transcription factor 3 (Foxp3) is critical transcription factor in CD4(+)CD25(+) regulatory T cells. There are increasing evidences that the functions of Foxp3 proteins are not restricted to regulatory T cells. The aim of this study is to evaluate the functions of Foxp3 proteins in LPS induced lung inflammation. In this study, LPS was administrated to Balb/c mice to induce a disease that resembles COPD. Two days prior to LPS administration, mice were infected once with the Foxp3-GFP or control GFP expression adenovirus to intra-trachea. The total cells and neutrophil numbers in bronchoalveolar lavage (BAL) fluid were counted and pro-inflammatory cytokine levels in BAL fluid were measured after 3 days later from LPS administration. Lung tissues were stained with hematoxylin and eosin (H&E) for histologic evaluation. Total cells, including eosinophil, macrophage and lymphocytes was significantly reduced in the foxp3 expression adenovirus infected mouse BAL fluid compared with the control adenovirus infected mouse BAL fluid. Foxp3-GFP or GFP was only detected in the lung epithelial cells by confocal microscopy. Using a mouse lung epithelial cell line, LA-4, Foxp3 adenovirus infected cells reduced the expression of chemokines such as CCL3, CXCL2 and CXCL5 by LPS stimulation. These results suggest that Foxp3 expression in lung epithelial cells suppresses inflammation via inhibition of chemokines secretion in lung inflammation.