PMID- 9703499
OWN - NLM
STAT- MEDLINE
DCOM- 19980825
LR  - 20220225
IS  - 0036-8075 (Print)
IS  - 0036-8075 (Linking)
VI  - 281
IP  - 5379
DP  - 1998 Aug 14
TI  - Feedback inhibition of macrophage tumor necrosis factor-alpha production by 
      tristetraprolin.
PG  - 1001-5
AB  - Tumor necrosis factor-alpha (TNF-alpha) is a major mediator of both acute and 
      chronic inflammatory responses in many diseases. Tristetraprolin (TTP), the 
      prototype of a class of Cys-Cys-Cys-His (CCCH) zinc finger proteins, inhibited 
      TNF-alpha production from macrophages by destabilizing its messenger RNA. This 
      effect appeared to result from direct TTP binding to the AU-rich element of the 
      TNF-alpha messenger RNA. TTP is a cytosolic protein in these cells, and its 
      biosynthesis was induced by the same agents that stimulate TNF-alpha production, 
      including TNF-alpha itself. These findings identify TTP as a component of a 
      negative feedback loop that interferes with TNF-alpha production by destabilizing 
      its messenger RNA. This pathway represents a potential target for anti-TNF-alpha 
      therapies.
FAU - Carballo, E
AU  - Carballo E
AD  - Office of Clinical Research and Laboratory of Signal Transduction, National 
      Institute of Environmental Health Sciences, Research Triangle Park, NC 27709, 
      USA.
FAU - Lai, W S
AU  - Lai WS
FAU - Blackshear, P J
AU  - Blackshear PJ
LA  - eng
PT  - Journal Article
PL  - United States
TA  - Science
JT  - Science (New York, N.Y.)
JID - 0404511
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (Immediate-Early Proteins)
RN  - 0 (Lipopolysaccharides)
RN  - 0 (Proteins)
RN  - 0 (RNA Probes)
RN  - 0 (RNA, Messenger)
RN  - 0 (Tristetraprolin)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 0 (ZFP36 protein, human)
RN  - 0 (Zfp36 protein, mouse)
SB  - IM
MH  - 3T3 Cells
MH  - Animals
MH  - Base Sequence
MH  - Biological Transport
MH  - Cell Line
MH  - Cell Nucleus/metabolism
MH  - Chick Embryo
MH  - Cytosol/metabolism
MH  - *DNA-Binding Proteins
MH  - Feedback
MH  - Gene Expression Regulation
MH  - Humans
MH  - *Immediate-Early Proteins
MH  - Lipopolysaccharides/pharmacology
MH  - Macrophages/*physiology
MH  - Mice
MH  - Mice, Knockout
MH  - Proteins/*physiology
MH  - RNA Probes
MH  - RNA, Messenger/chemistry/genetics/metabolism
MH  - Transfection
MH  - Tristetraprolin
MH  - Tumor Necrosis Factor-alpha/antagonists & inhibitors/*biosynthesis/genetics
MH  - *Zinc Fingers
EDAT- 1998/08/14 00:00
MHDA- 1998/08/14 00:01
CRDT- 1998/08/14 00:00
PHST- 1998/08/14 00:00 [pubmed]
PHST- 1998/08/14 00:01 [medline]
PHST- 1998/08/14 00:00 [entrez]
AID - 10.1126/science.281.5379.1001 [doi]
PST - ppublish
SO  - Science. 1998 Aug 14;281(5379):1001-5. doi: 10.1126/science.281.5379.1001.