PMID- 2123888 OWN - NLM STAT- MEDLINE DCOM- 19910122 LR - 20181113 IS - 0021-9738 (Print) IS - 0021-9738 (Linking) VI - 86 IP - 6 DP - 1990 Dec TI - Tumor necrosis factor-alpha inhibits expression of pulmonary surfactant protein. PG - 1954-60 AB - Tumor necrosis factor-alpha (TNF-alpha) decreased the expression of pulmonary surfactant proteins SP-A and SP-B in human pulmonary adenocarcinoma cell lines. The effect of TNF alpha on SP-A content and mRNA in the pulmonary adenocarcinoma cell line, H441-4, was concentration and time dependent. TNF alpha decreased the cellular content of SP-A to less than 10% of control 48 h after addition. TNF alpha decreased de novo synthesis of SP-A and decreased the accumulation of SP-A in media. SP-A mRNA was decreased within 12 h of addition of TNF alpha, with nearly complete loss of SP-A mRNA observed after 24 h. Inhibitory effects of TNF alpha on SP-A mRNA were dose-related with nearly complete inhibition of SP-A mRNA caused by 25 ng/ml TNF alpha. The effects of TNF alpha on SP-A were distinct from the effects of interferon gamma which increased SP-A content approximately twofold in H441-4 cells. TNF alpha also decreased the content of SP-B mRNA. In contrast to the inhibitory effect of TNF alpha on SP-A and SP-B mRNA, TNF alpha increased mRNA encoding human manganese superoxide dismutase (Mn-SOD). TNF alpha did not inhibit growth, alter cell viability or beta-actin mRNA in either cell line. These in vitro studies demonstrate the marked pretranslational inhibitory effects of the cytokine, TNF alpha, on the expression of pulmonary surfactant proteins, SP-A and SP-B. The results support the concept that macrophage-derived cytokines may control surfactant protein expression. FAU - Wispe, J R AU - Wispe JR AD - University of Cincinnati, Department of Pediatrics, Ohio 45267-0541. FAU - Clark, J C AU - Clark JC FAU - Warner, B B AU - Warner BB FAU - Fajardo, D AU - Fajardo D FAU - Hull, W E AU - Hull WE FAU - Holtzman, R B AU - Holtzman RB FAU - Whitsett, J A AU - Whitsett JA LA - eng GR - HL-28623/HL/NHLBI NIH HHS/United States GR - HL-39605/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 - J Clin Invest JT - The Journal of clinical investigation JID - 7802877 RN - 0 (Proteolipids) RN - 0 (Pulmonary Surfactant-Associated Protein A) RN - 0 (Pulmonary Surfactant-Associated Proteins) RN - 0 (Pulmonary Surfactants) RN - 0 (RNA, Messenger) RN - 0 (Tumor Necrosis Factor-alpha) RN - 82115-62-6 (Interferon-gamma) RN - EC 1.15.1.1 (Superoxide Dismutase) SB - IM MH - Blotting, Northern MH - Epithelium/metabolism MH - Gene Expression/drug effects MH - Humans MH - In Vitro Techniques MH - Interferon-gamma/pharmacology MH - Lung/cytology/*metabolism MH - Proteolipids/genetics/*metabolism MH - Pulmonary Surfactant-Associated Protein A MH - Pulmonary Surfactant-Associated Proteins MH - Pulmonary Surfactants/genetics/*metabolism MH - RNA, Messenger/genetics MH - Superoxide Dismutase/genetics MH - Tumor Cells, Cultured MH - Tumor Necrosis Factor-alpha/*pharmacology PMC - PMC329831 EDAT- 1990/12/01 00:00 MHDA- 1990/12/01 00:01 PMCR- 1990/12/01 CRDT- 1990/12/01 00:00 PHST- 1990/12/01 00:00 [pubmed] PHST- 1990/12/01 00:01 [medline] PHST- 1990/12/01 00:00 [entrez] PHST- 1990/12/01 00:00 [pmc-release] AID - 10.1172/JCI114929 [doi] PST - ppublish SO - J Clin Invest. 1990 Dec;86(6):1954-60. doi: 10.1172/JCI114929.