C/EBPb在由脂多醣引發的間白素-6基因轉錄調控的角色 與活化機制的探討
C/EBPb isoforms and their activity regulation by redox switch in lipopolysaccharide-inducible expression of Interleukin-6 gene
Date Issued
2004
Date
2004
Author(s)
Su, Wen-Chi
DOI
en-US
Abstract
C/EBPb is one of the key transcription factors responsible for the induction of genes involved in inflammatory response. NF-kB is another well-known crucial factor essential for controlling inflammatory cytokine genes expression. These two proteins have been reported to regulate IL-6 gene expression synergistically at the transcription level. However, the exact mechanism through which IL-6 expression is regulated remains uncharacterized. By treating cells with specific inhibitors of NF-kB or knock down the endogenous level of C/EBPb, we have demonstrated that these two proteins may have regulatory roles in IL-6 gene induction during inflammation in cell type-specific manner. In RAW264.7 cells, NF-kB plays predominant roles in activating IL-6 gene upon treatment with LPS while in p388D1(IL1) cells, C/EBPb is apparently more important than NF-kB.
C/EBPb has three isoforms, including two transcription activators (LAP* and LAP) and one transcription repressor (LIP). In addition to demonstrating the role of C/EBPb in IL-6 gene induction, we provide evidence that the transcriptional activities of one of the C/EBPb isoforms, LAP*, may be governed by the redox state of the cell. The DNA binding activity and transcriptional activation of LAP* are induced under reducing condition. The 11th amino acid (Cys-11) of LAP* may function as a molecular sensor of redox state that regulates the activity of LAP* toward activating its target genes. The LAP and LIP isoforms of C/EBPb, lacking 21 and 151 amino acids, respectively, are not modulated in a similar redox-responsive manner. Taken together, our observations provide evidence that LAP* is the primary isoform of C/EBPb that regulates, through a redox switch, the LPS-induced expression of the IL-6 gene in P388D1 cells.
Subjects
脂多醣 間白素-6 基因轉錄調控
C/EBPb isoforms redox lipopolysaccharide Interleuk
Type
other