PMID- 8048538 OWN - NLM STAT- MEDLINE DCOM- 19940830 LR - 20180109 IS - 0002-9513 (Print) IS - 0002-9513 (Linking) VI - 267 IP - 1 Pt 1 DP - 1994 Jul TI - 3'-untranslated region of SP-B mRNA mediates inhibitory effects of TPA and TNF-alpha on SP-B expression. PG - L16-24 AB - Surfactant protein-B (SP-B) is a small hydrophobic polypeptide that enhances spreading and stability of surfactant phospholipids in the alveolus of the lung. Decreased expression of SP-B is associated with respiratory failure in premature infants and in adult patients with acute respiratory distress syndrome (ARDS). Tumor necrosis factor-alpha (TNF-alpha) and 12-O-tetradecanoylphorbol-13 acetate (TPA) cause ARDS-like lung injury in vivo. Inhibitory effects of TPA and TNF-alpha on SP-B mRNA expression in vitro were mediated by decreased SP-B mRNA stability rather than by decreased rate of SP-B gene transcription. In the present study, a human pulmonary adenocarcinoma cell line, NCI H441-4, was stably transfected with expression vectors consisting of the thymidine kinase (TK) promotor and human growth hormone (hGH) gene, in which the hGH 3'-untranslated region (3'-UTR) was replaced by the 2.0-kb human SP-B cDNA [pTKGH(SP-B2.0)] or the 837-bp human SP-B 3'-UTR [pTKGH(SP-B.837)]. The mRNAs and cellular growth hormone protein generated from the chimeric TKGH(SP-B2.0) and TKGH(SP-B.837) genes were each inhibited by approximately 50% by TPA and TNF-alpha. Dexamethasone decreased the inhibitory effects of TPA and TNF-alpha. The inhibition of steady-state hGH-SP-B mRNA by TPA and TNF-alpha was mediated by a cis-active element located in the 3-UTR region of SP-B mRNA. FAU - Pryhuber, G S AU - Pryhuber GS AD - Division of Pulmonary Biology, Children's Hospital Medical Center, Cincinnati, Ohio 45229-3039. FAU - Church, S L AU - Church SL FAU - Kroft, T AU - Kroft T FAU - Panchal, A AU - Panchal A FAU - Whitsett, J A AU - Whitsett JA LA - eng GR - HL-38859/HL/NHLBI NIH HHS/United States GR - HL-41496/HL/NHLBI NIH HHS/United States PT - Journal Article PT - Research Support, Non-U.S. Gov't PT - Research Support, U.S. Gov't, P.H.S. PL - United States TA - Am J Physiol JT - The American journal of physiology JID - 0370511 RN - 0 (Oligonucleotide Probes) RN - 0 (Proteolipids) RN - 0 (Pulmonary Surfactants) RN - 0 (RNA, Messenger) RN - 0 (Tumor Necrosis Factor-alpha) RN - 9002-72-6 (Growth Hormone) RN - NI40JAQ945 (Tetradecanoylphorbol Acetate) SB - IM MH - Base Sequence MH - Growth Hormone/genetics/metabolism MH - Humans MH - Molecular Sequence Data MH - Oligonucleotide Probes/genetics MH - Protein Biosynthesis MH - Proteolipids/*genetics/*metabolism MH - Pulmonary Surfactants/*genetics/*metabolism MH - RNA, Messenger/*physiology MH - Tetradecanoylphorbol Acetate/pharmacology MH - Tumor Cells, Cultured MH - Tumor Necrosis Factor-alpha/*pharmacology EDAT- 1994/07/01 00:00 MHDA- 1994/07/01 00:01 CRDT- 1994/07/01 00:00 PHST- 1994/07/01 00:00 [pubmed] PHST- 1994/07/01 00:01 [medline] PHST- 1994/07/01 00:00 [entrez] AID - 10.1152/ajplung.1994.267.1.L16 [doi] PST - ppublish SO - Am J Physiol. 1994 Jul;267(1 Pt 1):L16-24. doi: 10.1152/ajplung.1994.267.1.L16.