RETINOIC ACID RECEPTOR ACTIVATION OF SP-B GENE-TRANSCRIPTION IN RESPIRATORY EPITHELIAL-CELLS

Retinoids are known to play important roles in organ development of th e lung. Retinoids exert their activity by modulating the expression of numerous genes, generally influencing gene transcription, in target c ells. In the present work, the mechanism by which retinoic acid (RA) r egulates surfactant protein (SP) B expression was assessed in vitro. R A (9-cis-RA) enhanced SP-B mRNA in pulmonary adenocarcinoma cells (H44 1 cells) and increased transcriptional activity of the SP-B promoter i n both 1-1441 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 respo nse of the SP-B promoter to RA. Treatment of H441 cells with RA increa sed immunostaining for the SP-B proprotein and increased the number of cells in which the SP-B proprotein was detected. An RA responsive ele ment mediating RA stimulation of the human SP-B promoter was identifie d. RAR-alpha and -gamma and RXR-alpha but not RAR-beta or RXR-beta and -gamma were detected by immunohistochemical analysis of H441 cells. R A, by activating RAR activity, stimulated the transcription and synthe sis of SP-B in pulmonary adenocarcinoma cells.