Transforming growth factor-beta inhibits surfactant protein A expression in vitro.
Effects of members of the transforming growth factor-beta (TGF-beta) family on expression of surfactant protein A (SP-A) were determined in human pulmonary adenocarcinoma cells. TGF-beta decreased SP-A content in two distinct pulmonary adenocarcinoma cell lines with bronchiolar (NCI-H441-4) and alveolar (NCI-H820) cell characteristics. TGF-beta 1, beta 2 and beta 3 were equally effective in decreasing SP-A. Effects of the TGF-beta's on SP-A content were dose dependent, EC50 approximately 20-30 pg/ml for each form of TGF-beta. TGF-beta decreased cellular SP-A content in association with decreased levels of SP-A mRNA. Inhibitory effects of TGF-beta 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-beta 1. TGF-beta-dependent inhibition of SP-A expression was not associated with altered cell morphology, growth, or viability. TGF-beta 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.
Whitsett
J A
JA
Division of Pulmonary Biology, Children's Hospital Medical Center, Cincinnati, OH.
Budden
A
A
Hull
W M
WM
Clark
J C
JC
O'Reilly
M A
MA
D000230:Adenocarcinoma; D015152:Blotting, Northern; D002455:Cell Division; D002470:Cell Survival; D015870:Gene Expression; D006801:Humans; D011510:Proteolipids / Q000096:biosynthesis* / Q000235:genetics; D037662:Pulmonary Surfactant-Associated Protein A; D037661:Pulmonary Surfactant-Associated Proteins; D011663:Pulmonary Surfactants / Q000096:biosynthesis* / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
D011510:Proteolipids; D037662:Pulmonary Surfactant-Associated Protein A; D037661:Pulmonary Surfactant-Associated Proteins; D011663:Pulmonary Surfactants; D012333:RNA, Messenger; D016212:Transforming Growth Factor beta