Rehli, Michael and Poltorak, Alexander and Schwarzfischer, Lucia and Krause, Stefan W. and Andreesen, Reinhard and Beutler, Bruce (2000) PU.1 and interferon consensus sequence-binding protein regulate the myeloid expression of the human toll-like receptor 4 gene. JOURNAL OF BIOLOGICAL CHEMISTRY, 275 (13). pp. 9773-9781. ISSN 0021-9258, 1083-351X
Full text not available from this repository. (Request a copy)Abstract
The protein product of the Toll-like receptor (TLR) 4 gene has been implicated in the signal transduction events induced by lipopolysaccharide (LPS). In mice, destructive mutations of Tlr4 impede the normal response to LPS and cause a high susceptibility to Gramnegative infection. Expression of TLR4 mRNA in humans is restricted to a small number of cell types, including LPS-responsive myeloid cells, B-cells, and endothelial cells. To investigate the molecular basis for TLR4 expression in cells of myeloid origin, we cloned the human TLR4 gene and analyzed its putative 5'-proximal promoter. In transient transfections a region of only 75 base pairs upstream of the major transcription initiation site was sufficient to induce maximal luciferase activity in THP-I cells, The sequence of this region is similar in human and mouse TLR4 genes and lacks a TATA box, typical Spl-sites or CCAAT box sequences. Instead, it contains consensus-binding sites for Ets family transcription factors, octamer-binding factors, and a composite interferon response factor/Ets motif. The activity of the promoter in macrophages was strictly dependent on the integrity of both half sites of the composite interferon response factor/Ets motif, which was constitutively bound by the myeloid and B-cell-specific transcription factor PU.1 and interferon consensus sequence-binding protein. These results indicate that the two tissue-restricted transcription factors PU.1 and interferon consensus sequence-binding protein participate in the basal regulation of human TLR4 in myeloid cells. Cloning of the human TLR4 gene provides a basis for further investigation of the possible impact of genetic variations on the susceptibility to infection and sepsis.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | TUMOR-NECROSIS-FACTOR; FACTOR KAPPA-B; TRANSCRIPTION FACTOR; DROSOPHILA TOLL; FAMILY MEMBER; MACROPHAGE TRANSCRIPTION; INTERLEUKIN-1 RECEPTOR; ENDOTOXIN RESISTANCE; GAMMA-INTERFERON; IL-1 RECEPTOR; |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Abteilung für Pädiatrische Hämatologie, Onkologie und Stammzelltransplantation |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 24 May 2022 08:34 |
| Last Modified: | 24 May 2022 08:34 |
| URI: | https://pred.uni-regensburg.de/id/eprint/42722 |
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