PMID- 8631819
OWN - NLM
STAT- MEDLINE
DCOM- 19960703
LR  - 20210210
IS  - 0021-9258 (Print)
IS  - 0021-9258 (Linking)
VI  - 271
IP  - 13
DP  - 1996 Mar 29
TI  - Inhibition of macrophage scavenger receptor activity by tumor necrosis 
      factor-alpha is transcriptionally and post-transcriptionally regulated.
PG  - 7767-73
AB  - Regulation of expression of the scavenger receptor is thought to play a critical 
      role in the accumulation of lipid by macrophages in atherosclerosis. Tumor 
      necrosis factor-alpha (TNF-alpha) has been shown to suppress macrophage scavenger 
      receptor function (van Lenten, B.J., and Fogelman, A.M. (1992) J. Immunol. 148, 
      112-6). However, the mechanism by which it does so is unknown. We evaluated the 
      mechanism by which TNF-alpha inhibited macrophage scavenger receptor surface 
      expression and binding of acetylated low density lipoprotein (aLDL). Binding of 
      aLDL to phorbol 12-myristate 13-acetate (PMA)-differentiated THP-1 macrophages 
      was suppressed by TNF-alpha in a dose-dependent manner. Inhibition of aLDL 
      binding was paralleled by a reduction of macrophage scavenger receptor protein as 
      detected by the Western blot. TNF-alpha partially decreased macrophage scavenger 
      receptor mRNA steady state levels in PMA-differentiated THP-1 macrophages, a 
      result that was confirmed by reverse transcription-polymerase chain reaction. PMA 
      increased the luciferase activity driven by the macrophage scavenger receptor 
      promoter in the transfected cells, whereas TNF-alpha partially reduced luciferase 
      activity. However, macrophage scavenger receptor mRNA half-life was dramatically 
      reduced in cells treated with TNF-alpha relative to untreated cells. Reduction in 
      macrophage scavenger receptor message in response to TNF-alpha was dependent on 
      new protein synthesis because it was blocked by cycloheximide. These results 
      indicate that TNF-alpha regulates macrophage scavenger receptor expression in 
      PMA-differentiated THP-1 macrophages by transcriptional and post-transcriptional 
      mechanisms but principally by destabilization of macrophage scavenger receptor 
      mRNA.
FAU - Hsu, H Y
AU  - Hsu HY
AD  - Department of Medicine, Cornell University Medical College, New York, 10021, USA.
FAU - Nicholson, A C
AU  - Nicholson AC
FAU - Hajjar, D P
AU  - Hajjar DP
LA  - eng
GR  - HL-46403/HL/NHLBI NIH HHS/United States
GR  - HL-49666/HL/NHLBI NIH HHS/United States
GR  - K14 HL-03158/HL/NHLBI NIH HHS/United States
GR  - etc.
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - J Biol Chem
JT  - The Journal of biological chemistry
JID - 2985121R
RN  - 0 (Lipoproteins, LDL)
RN  - 0 (Membrane Proteins)
RN  - 0 (Oleic Acids)
RN  - 0 (RNA, Messenger)
RN  - 0 (Receptors, Immunologic)
RN  - 0 (Receptors, LDL)
RN  - 0 (Receptors, Lipoprotein)
RN  - 0 (Receptors, Scavenger)
RN  - 0 (Recombinant Proteins)
RN  - 0 (Scarb1 protein, mouse)
RN  - 0 (Scavenger Receptors, Class B)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 2UMI9U37CP (Oleic Acid)
RN  - 98600C0908 (Cycloheximide)
RN  - EC 1.13.12.- (Luciferases)
RN  - NI40JAQ945 (Tetradecanoylphorbol Acetate)
SB  - IM
MH  - Blotting, Northern
MH  - Cell Differentiation
MH  - Cell Line
MH  - Cycloheximide/pharmacology
MH  - Dose-Response Relationship, Drug
MH  - *Gene Expression Regulation/drug effects
MH  - Humans
MH  - Kinetics
MH  - Lipoproteins, LDL/metabolism
MH  - Luciferases
MH  - Macrophages/drug effects/*immunology
MH  - *Membrane Proteins
MH  - Oleic Acid
MH  - Oleic Acids/metabolism
MH  - Polymerase Chain Reaction
MH  - Protein Biosynthesis/*drug effects
MH  - RNA, Messenger/biosynthesis/drug effects/metabolism
MH  - Receptors, Immunologic/antagonists & inhibitors/*biosynthesis
MH  - Receptors, LDL/drug effects/*metabolism
MH  - *Receptors, Lipoprotein
MH  - Receptors, Scavenger
MH  - Recombinant Proteins/pharmacology
MH  - Scavenger Receptors, Class B
MH  - Tetradecanoylphorbol Acetate/pharmacology
MH  - Transcription, Genetic/*drug effects
MH  - Transfection
MH  - Tumor Necrosis Factor-alpha/*pharmacology
EDAT- 1996/03/29 00:00
MHDA- 1996/03/29 00:01
CRDT- 1996/03/29 00:00
PHST- 1996/03/29 00:00 [pubmed]
PHST- 1996/03/29 00:01 [medline]
PHST- 1996/03/29 00:00 [entrez]
AID - S0021-9258(17)45190-8 [pii]
AID - 10.1074/jbc.271.13.7767 [doi]
PST - ppublish
SO  - J Biol Chem. 1996 Mar 29;271(13):7767-73. doi: 10.1074/jbc.271.13.7767.