PMID- 14991611
OWN - NLM
STAT- MEDLINE
DCOM- 20040325
LR  - 20170726
IS  - 0014-2980 (Print)
IS  - 0014-2980 (Linking)
VI  - 34
IP  - 3
DP  - 2004 Mar
TI  - Regulation of human IL-18 gene expression: interaction of PU.1 with GC-box 
      binding protein is involved in human IL-18 expression in myeloid cells.
PG  - 817-826
LID - 10.1002/eji.200324420 [doi]
AB  - Interleukin-18 (IL-18) is a pro-inflammatory cytokine which participates in host 
      defense against a variety of infections as well as in chronic inflammation 
      including autoimmune diseases. However, little is known about human IL-18 
      regulation at the gene level. We have previously demonstrated that sodium 
      butyrate, a bacterial fermentation product, induces IL-18 production via the 
      proximal region of the promoter. In this study we investigated the molecular 
      mechanisms for basal and sodium butyrate-induced expression of IL-18 in human 
      myeloid cells. Two regulatory regions, a consensus binding site for PU.1 and a 
      GC-rich region, are required for basal IL-18 promoter activity in human myeloid 
      cells. PU.1 bound to the PU.1 consensus binding site in electrophoretic mobility 
      shift assays, and overexpression of PU.1 led to activation of the IL-18 promoter 
      through this site. Mutation analysis revealed that the GC-rich region, but not 
      PU.1 site, participates in sodium butyrate-induced transactivation. Furthermore, 
      DNA pull-down experiments and the critical spacing of the two binding sites 
      suggest that formation of a protein complex involving both cis elements and the 
      respective binding proteins might be crucial for human IL-18 expression.
FAU - Koyama, Noriko
AU  - Koyama N
AD  - Department of Hematology, Johann Wolfgang Goethe University, Frankfurt, Germany.
FAU - Hoelzer, Dieter
AU  - Hoelzer D
AD  - Department of Hematology, Johann Wolfgang Goethe University, Frankfurt, Germany.
FAU - Ottmann, Oliver G
AU  - Ottmann OG
AD  - Department of Hematology, Johann Wolfgang Goethe University, Frankfurt, Germany.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - Germany
TA  - Eur J Immunol
JT  - European journal of immunology
JID - 1273201
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (Interleukin-18)
RN  - 0 (Proto-Oncogene Proteins)
RN  - 0 (Trans-Activators)
RN  - 0 (proto-oncogene protein Spi-1)
RN  - 9007-49-2 (DNA)
SB  - IM
MH  - Base Sequence
MH  - Cell Line
MH  - DNA/chemistry/metabolism
MH  - DNA-Binding Proteins/*metabolism
MH  - GC Rich Sequence
MH  - Gene Expression Regulation
MH  - Humans
MH  - Interleukin-18/biosynthesis/*genetics
MH  - Myeloid Cells/*immunology
MH  - Promoter Regions, Genetic
MH  - Proto-Oncogene Proteins/*metabolism
MH  - *Regulatory Sequences, Nucleic Acid
MH  - Trans-Activators/*metabolism
MH  - *Transcriptional Activation
MH  - U937 Cells
EDAT- 2004/03/03 05:00
MHDA- 2004/03/26 05:00
CRDT- 2004/03/03 05:00
PHST- 2004/03/03 05:00 [pubmed]
PHST- 2004/03/26 05:00 [medline]
PHST- 2004/03/03 05:00 [entrez]
AID - 10.1002/eji.200324420 [doi]
PST - ppublish
SO  - Eur J Immunol. 2004 Mar;34(3):817-826. doi: 10.1002/eji.200324420.