Dexamethasone Potentiates Keratinocyte Growth FactorStimulated SPA and SPB Gene Expression in Alveolar Epithelial Cells

Keratinocyte growth factor KGF, or fibroblast growth factor 7 was previously reported to enhance the synthesis of surfactant in alveolar type II cells. We investigated the possible interactions between KGF and a glucocorticoid, dexamethasone Dex, on surfactant protein SP gene expression. In cultured fetal rat type II cells, KGF and Dex induced greaterthanadditive stimulating effects on SPA and SPB expressions that were enhanced threefold and 30fold, respectively, but had only additive effects on SPC expression. Using murine lung epithelial MLE cells, KGF increased SPA, SPB up to twofold, and SPC up to threefold mRNA levels in a dosedependent way. Dex 10−9to 10−7M increased SPA and SPB mRNA 1.5fold and SPC mRNA twofold. Consistent with type II cell findings, simultaneous treatment by KGF and Dex induced a synergistic increase of SPA and SPB transcripts threefold and 4.5fold, respectively, but not of SPC transcripts. SPA protein was present in MLE15 and was increased about threefold by KGF plus Dex. Expression study of a reporter gene placed under either the SPA or the SPB gene regulatory sequences and transfected in MLE15 cells indicated that the DexKGF synergy was achieved mainly through a transcriptional effect for SPA, and both transcriptional and nontranscriptional effects for SPB. For the latter, increased mRNA stability was evidenced with the aid of actinomycin D. The DexKGF synergy may have potential interest for diseases associated with surfactant deficiency.