PMID- 1712776
OWN - NLM
STAT- MEDLINE
DCOM- 19910819
LR  - 20210210
IS  - 0021-9258 (Print)
IS  - 0021-9258 (Linking)
VI  - 266
IP  - 20
DP  - 1991 Jul 15
TI  - Glucocorticoids inhibit the transcriptional induction of JE, a platelet-derived 
      growth factor-inducible gene.
PG  - 13261-6
AB  - Macrophages and monocytes have essential roles in normal wound healing, in the 
      immune response, and in the pathogenesis of atherosclerosis. Platelet-derived 
      growth factor (PDGF) stimulates the transcription of the early response gene, JE, 
      and its human homolog, macrophage chemotactic protein-1 (MCP-1) in fibroblasts. 
      JE/MCP-1 encodes a cytokine which is a member of a superfamily of small inducible 
      genes that include platelet factor 4, beta-thromboglobulin, 310-C/NAP-1/IL-8, 
      IP-10, KC/gro/MGSA, and others which may play important roles in the inflammatory 
      and immune response. We now report that glucocorticoids inhibit the 
      transcriptional induction of the JE gene by PDGF and serum in a dose-dependent 
      manner. The glucocorticoid response followed the expected anti-inflammatory rank 
      order of potency and was not due to a shift in the time course of induction. 
      Nonsteroidal anti-inflammatory agents were ineffective in reducing JE mRNA 
      levels. Dexamethasone inhibited the accumulation of JE transcripts induced by 
      PDGF, 12-O-tetradecanoylphorbol-13-acetate, and double-stranded synthetic RNA. 
      Nuclear runoff assays demonstrated that the negative regulation occurred by 
      decreasing the transcriptional induction of the JE gene. No effects on JE message 
      stability could be detected in the presence of dexamethasone. The protein 
      synthesis inhibitors cycloheximide and puromycin reversed the 
      glucocorticoid-mediated inhibition and suggested that new protein synthesis was 
      necessary. These results suggest that the transcriptional inhibition of 
      glucocorticoids is mediated by the expression of a labile transcriptional 
      repressor for the JE gene.
FAU - Kawahara, R S
AU  - Kawahara RS
AD  - Department of Medicine, Jewish Hospital, Washington University Medical Center, 
      St. Louis, Missouri 63110.
FAU - Deng, Z W
AU  - Deng ZW
FAU - Deuel, T F
AU  - Deuel TF
LA  - eng
GR  - CA49712/CA/NCI NIH HHS/United States
GR  - HL14147/HL/NHLBI NIH HHS/United States
GR  - HL31102/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  - J Biol Chem
JT  - The Journal of biological chemistry
JID - 2985121R
RN  - 0 (Culture Media)
RN  - 0 (Cytokines)
RN  - 0 (Platelet-Derived Growth Factor)
RN  - 0 (RNA, Messenger)
RN  - 0 (Recombinant Proteins)
RN  - 63231-63-0 (RNA)
RN  - 7S5I7G3JQL (Dexamethasone)
RN  - X4W7ZR7023 (Methylprednisolone)
SB  - IM
GS  - JE
MH  - Animals
MH  - Blotting, Northern
MH  - Cell Line
MH  - Cell Nucleus/physiology
MH  - Culture Media
MH  - Cytokines/*genetics
MH  - Dexamethasone/*pharmacology
MH  - Dose-Response Relationship, Drug
MH  - Genes/*drug effects
MH  - Methylprednisolone/*pharmacology
MH  - Mice
MH  - Mice, Inbred BALB C
MH  - Platelet-Derived Growth Factor/*pharmacology
MH  - RNA/genetics/isolation & purification
MH  - RNA, Messenger/drug effects/genetics/isolation & purification
MH  - Recombinant Proteins/pharmacology
MH  - Transcription, Genetic/*drug effects
EDAT- 1991/07/15 00:00
MHDA- 1991/07/15 00:01
CRDT- 1991/07/15 00:00
PHST- 1991/07/15 00:00 [pubmed]
PHST- 1991/07/15 00:01 [medline]
PHST- 1991/07/15 00:00 [entrez]
AID - S0021-9258(18)98832-0 [pii]
PST - ppublish
SO  - J Biol Chem. 1991 Jul 15;266(20):13261-6.