Regulation of lung surfactant protein gene expression.

Surfactant, a complex mixture of lipids and proteins, produced by the alveolar type II cells of the lung epithelium maintains alveolar integrity and plays important roles in the control of host defense and inflammation in the lung. Surfactant protein (SP) A, B, C and D genes are expressed in a cell-type restricted manner by the Clara and/or alveolar type II cells of the lung. Surfactant protein genes are independently regulated during fetal lung development and by hormones, cytokines and other agents. Transcriptional and/or posttranscriptional (mRNA stability) mechanisms control multifactorial regulation of surfactant protein gene expression. In vitro cell culture and transgenic animal studies have shown that relatively short promoter sequences control cell/tissue-specific expression and developmental regulation of surfactant protein genes. Surfactant protein promoter function is dependent on the combinatorial actions of multiple transcription factors, and thyroid transcription factor 1 (TTF-1/Nkx2.1) is a common positive regulator of surfactant protein promoter activity.