PMID- 1616052
OWN - NLM
STAT- MEDLINE
DCOM- 19920729
LR  - 20171213
IS  - 0002-9513 (Print)
IS  - 0002-9513 (Linking)
VI  - 262
IP  - 6 Pt 1
DP  - 1992 Jun
TI  - Effects of TNF-alpha and phorbol ester on human surfactant protein and MnSOD gene 
      transcription in vitro.
PG  - L688-93
AB  - Tumor necrosis factor-alpha (TNF-alpha) and the phorbol ester, 
      12-O-tetradecanoyl-phorbol-13-acetate (TPA) decrease the synthesis of surfactant 
      proteins association with decreased SP-A and SP-B mRNA. Nuclear run-on assays 
      were utilized to test whether the inhibitory effects of TNF-alpha and TPA were 
      associated with changes in surfactant protein gene transcription. SP-A gene 
      transcription was inhibited by both TNF-alpha and TPA as assessed by nuclear 
      run-on assays. Inhibitory effects of both agents on SP-A gene transcription were 
      readily detected within 6 h after exposure and persisted for 24 h. While 
      TNF-alpha and TPA decreased cellular SP-B mRNA content, transcription of the SP-B 
      gene was not influenced by these agents. In contrast to the inhibitory effects of 
      TPA and TNF-alpha on SP-A and SP-B mRNAs, steady-state mRNA and rate of 
      transcription of human manganese superoxide dismutase (MnSOD) were increased by 
      both agents. The time course and extent of increased MnSOD gene transcription by 
      TNF-alpha and TPA were distinct. Transcription of the human beta-actin gene was 
      not altered by either agent. The inhibitory effects of TPA and TNF-alpha on SP-A 
      expression in pulmonary adenocarcinoma cells are associated with the inhibition 
      of SP-A gene transcription. Loss of SP-B mRNA was not accompanied by decreased 
      SP-B gene transcription. Actinomycin D blocked the inhibitory effects of 
      TNF-alpha and TPA on SP-A and SP-B mRNA, supporting a role for 
      posttranscriptional events in the modulation of the expression of the surfactant 
      proteins SP-A and SP-B.
FAU - Whitsett, J A
AU  - Whitsett JA
AD  - Division of Pulmonary Biology, Children's Hospital Medical Center, Cincinnati, 
      Ohio 45229.
FAU - Clark, J C
AU  - Clark JC
FAU - Wispe, J R
AU  - Wispe JR
FAU - Pryhuber, G S
AU  - Pryhuber GS
LA  - eng
GR  - HL-28623/HL/NHLBI NIH HHS/United States
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 (DNA, Neoplasm)
RN  - 0 (Isoenzymes)
RN  - 0 (RNA, Messenger)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 1CC1JFE158 (Dactinomycin)
RN  - EC 1.15.1.1 (Superoxide Dismutase)
RN  - NI40JAQ945 (Tetradecanoylphorbol Acetate)
SB  - IM
MH  - Adenocarcinoma
MH  - Blotting, Northern
MH  - Cell Line
MH  - Cell Nucleus/drug effects/*physiology
MH  - Cloning, Molecular
MH  - DNA, Neoplasm/genetics/isolation & purification
MH  - Dactinomycin/pharmacology
MH  - Genes/drug effects
MH  - Humans
MH  - Isoenzymes/*genetics
MH  - Kinetics
MH  - Lung Neoplasms
MH  - RNA, Messenger/genetics/metabolism
MH  - Superoxide Dismutase/*genetics
MH  - Tetradecanoylphorbol Acetate/*pharmacology
MH  - Transcription, Genetic/*drug effects
MH  - Tumor Necrosis Factor-alpha/*pharmacology
EDAT- 1992/06/01 00:00
MHDA- 1992/06/01 00:01
CRDT- 1992/06/01 00:00
PHST- 1992/06/01 00:00 [pubmed]
PHST- 1992/06/01 00:01 [medline]
PHST- 1992/06/01 00:00 [entrez]
AID - 10.1152/ajplung.1992.262.6.L688 [doi]
PST - ppublish
SO  - Am J Physiol. 1992 Jun;262(6 Pt 1):L688-93. doi: 10.1152/ajplung.1992.262.6.L688.