PMID- 15640148
OWN - NLM
STAT- MEDLINE
DCOM- 20050419
LR  - 20210209
IS  - 0021-9258 (Print)
IS  - 0021-9258 (Linking)
VI  - 280
IP  - 10
DP  - 2005 Mar 11
TI  - Early growth response factor-1 mediates prostaglandin E2-dependent 
      transcriptional suppression of cytokine-induced tumor necrosis factor-alpha gene 
      expression in human macrophages and rheumatoid arthritis-affected synovial 
      fibroblasts.
PG  - 9536-46
AB  - Tumor necrosis factor-alpha (TNF-alpha) is a pleiotropic proinflammatory cytokine 
      that modulates a broad range of inflammatory and immunological processes. We have 
      investigated the potential immunomodulatory properties of prostaglandin E2 (PGE2) 
      by examining the molecular mechanism by which the eicosanoid suppresses 
      T-cell-derived interleukin-17 (IL-17)-induced TNF-alpha mRNA expression and 
      protein synthesis in human macrophages and rheumatoid arthritis-affected synovial 
      fibroblasts. Initial studies confirmed that PGE2 induces egr-1 mRNA expression 
      and protein synthesis by restricted SAPK2/p38 MAPK-dependent activating 
      transcription factor-2 (ATF-2) dimer transactivation of the egr-1 promoter as 
      judged by studies using wild-type (WT) and deletion mutant egr-1 promoter 
      constructs, Northern and Western blotting, and standard and supershift 
      electrophoretic mobility shift analyses. Using human leukemic monocytic THP-1 
      cells stably transfected with WT and dominant-negative mutant expression 
      constructs of Egr-1, cotransfected or not with a WT pTNF-615SVOCAT construct, we 
      observed that PGE2 inhibition of IL-17-stimulated TNF-alpha mRNA expression and 
      promoter activity was dependent on Egr-1 expression, as mutants of Egr-1, alone 
      or in combination, markedly abrogated any inhibitory effect of PGE2. Standard and 
      supershift electrophoretic mobility shift analysis, signaling "decoy" 
      overexpression studies, and pTNF-615SVOCAT promoter assays using WT and mutant 
      promoter constructs revealed that IL-17-up-regulated promoter activity was 
      largely dependent on ATF-2/c-Jun transactivation. PGE2 suppression of 
      IL-17-induced ATF-2/c-Jun transactivation and DNA binding was dependent on 
      Egr-1-mediated inhibition of induced c-Jun expression. We suggest that egr-1 is 
      an immediate-early PGE2 target gene that may be a key regulatory factor in 
      mediating eicosanoid control of genes involved in the immune and inflammatory 
      responses.
FAU - Faour, Wissam H
AU  - Faour WH
AD  - Department of Medicine, University of Ottawa, Ottawa, Ontario K1H 8M5, Canada.
FAU - Alaaeddine, Nada
AU  - Alaaeddine N
FAU - Mancini, Arturo
AU  - Mancini A
FAU - He, Qing Wen
AU  - He QW
FAU - Jovanovic, Dragan
AU  - Jovanovic D
FAU - Di Battista, John A
AU  - Di Battista JA
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20050107
PL  - United States
TA  - J Biol Chem
JT  - The Journal of biological chemistry
JID - 2985121R
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (EGR1 protein, human)
RN  - 0 (Early Growth Response Protein 1)
RN  - 0 (Immediate-Early Proteins)
RN  - 0 (Interleukin-17)
RN  - 0 (RNA, Messenger)
RN  - 0 (Recombinant Proteins)
RN  - 0 (Transcription Factors)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - K7Q1JQR04M (Dinoprostone)
SB  - IM
MH  - 3T3 Cells
MH  - Animals
MH  - Arthritis, Rheumatoid/blood/*immunology
MH  - Cells, Cultured
MH  - DNA-Binding Proteins/*genetics
MH  - Dinoprostone/*pharmacology
MH  - Early Growth Response Protein 1
MH  - Fibroblasts/immunology/physiology
MH  - HeLa Cells
MH  - Humans
MH  - Immediate-Early Proteins/*genetics
MH  - Interleukin-17/pharmacology
MH  - Macrophages/immunology
MH  - Mice
MH  - Monocytes/immunology
MH  - RNA, Messenger/genetics
MH  - Recombinant Proteins/pharmacology
MH  - Synovial Membrane/pathology
MH  - Transcription Factors/*genetics
MH  - Transcription, Genetic/drug effects
MH  - Tumor Necrosis Factor-alpha/genetics
EDAT- 2005/01/11 09:00
MHDA- 2005/04/20 09:00
CRDT- 2005/01/11 09:00
PHST- 2005/01/11 09:00 [pubmed]
PHST- 2005/04/20 09:00 [medline]
PHST- 2005/01/11 09:00 [entrez]
AID - S0021-9258(19)62973-X [pii]
AID - 10.1074/jbc.M414067200 [doi]
PST - ppublish
SO  - J Biol Chem. 2005 Mar 11;280(10):9536-46. doi: 10.1074/jbc.M414067200. Epub 2005 
      Jan 7.