Retinoic acid-receptor activation of SP-B gene transcription in respiratory epithelial cells

Abstract

Retinoids are known to play important roles in organ development of the lung. Retinoids exert their activity by modulating the expression of numerous genes, generally influencing gene transcription, in target cells. In the present work, the mechanism by which retinoic acid (RA) regulates surfactant protein (SP) B expression was assessed in vitro. RA (9-cis-RA) enhanced SP-B mRNA in pulmonary adenocarcinoma cells (H441 cells) and increased transcriptional activity of the SP-B promoter in both H441 and mouse lung epithelial cells (MLE-15). Cotransfection of H441 cells with retinoid nuclear receptor (RAR)-alpha, -beta, and -gamma and retinoid X receptor (RXR)-gamma further increased the response of the SP-B promoter to RA. Treatment of H441 cells with RA increased immunostaining for the SP-B proprotein and increased the number of cells in which the SP-B proprotein was detected. An RA responsive element mediating RA stimulation of the human SP-B promoter was identified. RAR-alpha and -gamma and RXR-alpha but not RAR-beta or RXR-beta and -gamma were detected by immunohistochemical analysis of H441 cells. RA, by activating RAR activity, stimulated the transcription and synthesis of SP-B in pulmonary adenocarcinoma cells.