PMID- 9759897
OWN - NLM
STAT- MEDLINE
DCOM- 19981022
LR  - 20081121
IS  - 0022-1767 (Print)
IS  - 0022-1767 (Linking)
VI  - 161
IP  - 7
DP  - 1998 Oct 1
TI  - A complex element regulates IFN-gamma-stimulated monocyte chemoattractant 
      protein-1 gene transcription.
PG  - 3719-28
AB  - Monocyte chemoattractant protein-1 (MCP-1) is induced in chronic osseous 
      inflammation, and is temporally and spatially correlated with monocyte 
      recruitment. We investigated the mechanism of MCP-1 regulation in a human 
      osteoblastic cell line in response to IFN-gamma, a potent mediator of the immune 
      inflammatory response. Nuclear run-on and stability studies demonstrated that 
      IFN-gamma stimulated MCP-1 transcription and did not enhance mRNA stabilization. 
      Using MCP-1 promoter/reporter gene constructs, we determined that 
      IFN-gamma-enhanced MCP-1 transcription is regulated by a 29-bp element located at 
      -227 relative to the ATG start codon. This element contains a 13-bp CT-rich 
      sequence (GCTTCCCTTTCCT) adjacent to a IFN-gamma activation site (GAS). Since 
      deletion of the CT sequence enhanced both the magnitude and duration of 
      IFN-gamma-stimulated, GAS-mediated transcription, we have termed it the IFN 
      response-inhibitory sequence (IRIS). The combined IRIS/GAS sequence is highly 
      conserved in mouse, rat, and bovine MCP-1 genes. In gel-shift assays, nuclear 
      extracts from IFN-gamma-stimulated osteoblastic cells formed two specific 
      inducible bands with labeled IRIS/GAS DNA. Both bands were supershifted by 
      anti-STAT1 Abs, but not by Abs to STAT2, p48(ISGF-3y), IFN-regulatory factor-1, 
      or IFN-regulatory factor-2. Formation of one of the bands required the presence 
      of the IRIS moiety. IRIS/GAS DNA also formed a number of specific complexes with 
      constitutively expressed factors, none of which were affected by the above Abs. 
      These studies establish a mechanism for IFN-gamma-stimulated MCP-1 expression and 
      identify a complex element that regulates MCP-1 gene transcription.
FAU - Valente, A J
AU  - Valente AJ
AD  - Department of Medicine, University of Texas Health Science Center, San Antonio 
      78284-7870, USA. valente@uthscsa.edu
FAU - Xie, J F
AU  - Xie JF
FAU - Abramova, M A
AU  - Abramova MA
FAU - Wenzel, U O
AU  - Wenzel UO
FAU - Abboud, H E
AU  - Abboud HE
FAU - Graves, D T
AU  - Graves DT
LA  - eng
GR  - DE07559/DE/NIDCR NIH HHS/United States
GR  - HL52665/HL/NHLBI NIH HHS/United States
GR  - L52665/PHS HHS/United States
GR  - etc.
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - J Immunol
JT  - Journal of immunology (Baltimore, Md. : 1950)
JID - 2985117R
RN  - 0 (Chemokine CCL2)
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (Nuclear Proteins)
RN  - 0 (Transcription Factors)
RN  - 82115-62-6 (Interferon-gamma)
SB  - IM
MH  - Base Sequence
MH  - Chemokine CCL2/*genetics
MH  - Conserved Sequence/immunology
MH  - DNA-Binding Proteins/metabolism
MH  - Evolution, Molecular
MH  - Gene Expression Regulation, Neoplastic/immunology
MH  - Humans
MH  - Interferon-gamma/*physiology
MH  - Molecular Sequence Data
MH  - Nuclear Proteins/metabolism
MH  - Osteoblasts/drug effects/metabolism
MH  - Promoter Regions, Genetic/immunology
MH  - Transcription Factors/genetics/physiology
MH  - Transcription, Genetic/drug effects/*immunology
MH  - Tumor Cells, Cultured
EDAT- 1998/10/06 00:00
MHDA- 1998/10/06 00:01
CRDT- 1998/10/06 00:00
PHST- 1998/10/06 00:00 [pubmed]
PHST- 1998/10/06 00:01 [medline]
PHST- 1998/10/06 00:00 [entrez]
PST - ppublish
SO  - J Immunol. 1998 Oct 1;161(7):3719-28.