Identification of the IL-6-responsive element in an acute-phase-responsive human pancreatic secretory trypsin inhibitor-encoding gene.
Pancreatic secretory trypsin inhibitor (PSTI) has been suggested to be an acute-phase reactant in humans and to be induced by inflammatory cytokines such as the interleukins IL-1 and IL-6. We report that PSTI is synthesized in hepatoma cells and that the gene expression is augmented by IL-6. The start points (tsp) for basal and augmented transcription are exactly the same as the tsp in normal pancreas. Analysis of the PSTI gene revealed that a 40-bp DNA fragment located between kb -3.84 and -3.80 carries the element responsible for both transcriptional activity and IL-6-induced gene expression. This 40-bp fragment contains TTGNNGNAATG, the consensus sequence for the NF-IL6-binding site, which is also known as the IL-6-responsive element that is conserved among various acute-phase genes. The basal activity was augmented by another sequence that lies between kb -4.0 and -3.9.
Yasuda
T
T
Department of Surgery II, Osaka University Medical School, Japan.
Ogawa
M
M
Murata
A
A
Ohmachi
Y
Y
Yasuda
T
T
Mori
T
T
Matsubara
K
K
D000209:Acute-Phase Proteins / Q000235:genetics*; D001483:Base Sequence; D006528:Carcinoma, Hepatocellular; D016384:Consensus Sequence; D004247:DNA; D006801:Humans; D015850:Interleukin-6 / Q000378:metabolism*; D008099:Liver / Q000378:metabolism; D008969:Molecular Sequence Data; D010179:Pancreas / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D012045:Regulatory Sequences, Nucleic Acid; D014158:Transcription, Genetic; D014359:Trypsin Inhibitor, Kazal Pancreatic / Q000235:genetics*; D014407:Tumor Cells, Cultured
D000209:Acute-Phase Proteins; D015850:Interleukin-6; D012333:RNA, Messenger; D014359:Trypsin Inhibitor, Kazal Pancreatic; D004247:DNA