PMID- 10748205
OWN - NLM
STAT- MEDLINE
DCOM- 20000630
LR  - 20210209
IS  - 0021-9258 (Print)
IS  - 0021-9258 (Linking)
VI  - 275
IP  - 21
DP  - 2000 May 26
TI  - The C/EBP bZIP domain can mediate lipopolysaccharide induction of the 
      proinflammatory cytokines interleukin-6 and monocyte chemoattractant protein-1.
PG  - 16373-81
AB  - C/EBPalpha, beta, and delta are all expressed by bone marrow-derived macrophages. 
      Ectopic expression of any of these transcription factors is sufficient to confer 
      lipopolysaccharide (LPS)-inducible expression of interleukin-6 (IL-6) and 
      monocyte chemoattractant protein-1 (MCP-1) to a B lymphoblast cell line, which 
      normally lacks C/EBP factors and does not display LPS induction of 
      proinflammatory cytokines. Thus, the activities of C/EBPalpha, beta, and delta 
      are redundant in regard to expression of IL-6 and MCP-1. Surprisingly, the bZIP 
      region of C/EBPbeta, which lacks any previously described activation domains, can 
      also confer LPS-inducible expression of IL-6 and MCP-1 in stable transfectants. 
      Transient transfections reveal that the bZIP regions of C/EBPbeta, C/EBPdelta, 
      and, to a lesser extent, C/EBPalpha can activate the IL-6 promoter and augment 
      its induction by LPS. Furthermore, the transdominant inhibitor, LIP, can activate 
      expression from the IL-6 promoter. The ability of the C/EBPbeta bZIP region to 
      activate the IL-6 promoter in transient transfections is completely dependent 
      upon an intact NF-kappaB-binding site, supporting a model where the bZIP protein 
      primarily functions to augment the activity of NF-kappaB. Replacement of the 
      leucine zipper of C/EBPbeta with that of GCN4 yields a chimeric protein that can 
      dimerize and specifically bind to a C/EBP consensus sequence, but shows a 
      markedly reduced ability to activate IL-6 and MCP-1 expression. These results 
      implicate the leucine zipper domain in some function other than dimerization with 
      known C/EBP family members, and suggest that C/EBP redundancy in regulating 
      cytokine expression may result from their highly related bZIP regions.
FAU - Hu, H M
AU  - Hu HM
AD  - Department of Microbiology, Michigan State University, East Lansing, Michigan 
      48824-1101, USA.
FAU - Tian, Q
AU  - Tian Q
FAU - Baer, M
AU  - Baer M
FAU - Spooner, C J
AU  - Spooner CJ
FAU - Williams, S C
AU  - Williams SC
FAU - Johnson, P F
AU  - Johnson PF
FAU - Schwartz, R C
AU  - Schwartz RC
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Biol Chem
JT  - The Journal of biological chemistry
JID - 2985121R
RN  - 0 (CCAAT-Enhancer-Binding Protein-beta)
RN  - 0 (CCAAT-Enhancer-Binding Proteins)
RN  - 0 (Chemokine CCL2)
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (Fungal Proteins)
RN  - 0 (Interleukin-6)
RN  - 0 (Lipopolysaccharides)
RN  - 0 (NF-kappa B)
RN  - 0 (Nuclear Proteins)
RN  - 0 (Protein Isoforms)
RN  - 0 (Recombinant Fusion Proteins)
RN  - 0 (Repressor Proteins)
RN  - 0 (Saccharomyces cerevisiae Proteins)
RN  - 0 (Transcription Factors)
RN  - EC 2.7.- (Protein Kinases)
SB  - IM
MH  - Animals
MH  - B-Lymphocytes
MH  - Binding Sites
MH  - CCAAT-Enhancer-Binding Protein-beta
MH  - CCAAT-Enhancer-Binding Proteins
MH  - Cell Line
MH  - Chemokine CCL2/*biosynthesis/genetics
MH  - DNA-Binding Proteins/genetics/*metabolism
MH  - Dimerization
MH  - Fungal Proteins/genetics
MH  - Gene Expression Regulation
MH  - Interleukin-6/*biosynthesis/genetics
MH  - Leucine Zippers/*genetics
MH  - Lipopolysaccharides/*pharmacology
MH  - Mice
MH  - NF-kappa B/metabolism
MH  - Nuclear Proteins/analysis/genetics/*metabolism
MH  - Promoter Regions, Genetic
MH  - Protein Isoforms/metabolism
MH  - Protein Kinases/genetics
MH  - Recombinant Fusion Proteins/genetics
MH  - Repressor Proteins/pharmacology
MH  - *Saccharomyces cerevisiae Proteins
MH  - Transcription Factors/genetics/*metabolism
MH  - Transcriptional Activation
MH  - Transfection
EDAT- 2000/04/05 09:00
MHDA- 2000/07/08 11:00
CRDT- 2000/04/05 09:00
PHST- 2000/04/05 09:00 [pubmed]
PHST- 2000/07/08 11:00 [medline]
PHST- 2000/04/05 09:00 [entrez]
AID - S0021-9258(19)80439-8 [pii]
AID - 10.1074/jbc.M910269199 [doi]
PST - ppublish
SO  - J Biol Chem. 2000 May 26;275(21):16373-81. doi: 10.1074/jbc.M910269199.