Transforming growth factor-β inhibits surfactant protein A expression in vitro

Abstract

Effects of members of the transforming growth factor-β (TGF-β) family on expression of surfactant protein A (SP-A) were determined in human pulmonary adenocarcinoma cells. TGF-β decreased SP-A content in two distinct pulmonary adenocarcinoma cell lines with bronchiolar (NCI-H441-4) and alveolar (NCI-H820) cell characteristics. TGF- β 1, β 2 and β 3 were equally effective in decreasing SP-A. Effects of the TGF-β's on SP-A content were dose dependent, EC 50 approximately 20–30 pg/ml for each form of TGF-β. TGF-β decreased cellular SP-A content in association with decreased levels of SP-A mRNA. Inhibitory effects of TGF- β 1, on SP-A mRNA was time dependent, reaching maximal effects within 12–24 h, after which SP-A mRNA was approximately 10% of that present in untreated cells. Maximal inhibition of SP-A mRNA was observed at 250 pg/ml TGF- β 1. TGF-β-dependent inhibition of SP-A expression was not associated with altered cell morphology, growth, or viability. TGF-β family members act directly on pulmonary adenocarcinoma cells to inhibit SP-A expression by mechanisms which are mediated, at least in part, at a pretranslational level.