Interleukin-10 activates heat-shock protein 90beta gene expression
| Autor: | David A. Isenberg, Anastasis Stephanou, B. J. M. Ripley, David S. Latchman |
|---|---|
| Rok vydání: | 1999 |
| Předmět: |
STAT3 Transcription Factor
medicine.medical_treatment Immunology Cell Culture Techniques Biology Heat shock protein Gene expression medicine Tumor Cells Cultured Immunology and Allergy Humans HSP90 Heat-Shock Proteins Transcription factor Reporter gene Promoter Original Articles Molecular biology Recombinant Proteins Interleukin-10 Up-Regulation DNA-Binding Proteins Interleukin 10 Cytokine STAT protein Leukocytes Mononuclear Trans-Activators Acute-Phase Proteins |
| Zdroj: | Immunology. 97(2) |
| ISSN: | 0019-2805 |
| Popis: | Elevated levels of the cytokine interleukin-10 (IL-10) have been reported in patients with active systemic lupus erythematosus (SLE). Any role for IL-10 in the pathogenesis of SLE is likely to involve the activation of expression of specific genes within its target cells. We have previously reported elevated levels of the 90000 MW heat-shock protein (hsp 90) and autoantibodies to hsp 90 in patients with SLE. Recent studies have shown that the cytokine IL-6 activates hsp 90 gene expression via specific transcription factors that include STAT-3 (signal transducer and activator of transcription 3). In view of the known role of STAT proteins in IL-10 signalling pathways, we have investigated the effect of IL-10 on hsp 90 gene expression. Here we report that IL-10 enhances the expression of hsp 90 in both a human hepatoma cell line (HepG2) stably expressing the human IL-10 receptor and peripheral blood mononuclear cells (PBMC). In reporter gene assays IL-10 is able to activate both the hsp 90 alpha and hsp 90 beta promoters directly. Furthermore, a short region of the hsp 90 beta promoter which is activated in response to IL-10, contains a STAT-3 binding site. This element but not a mutant derivative unable to bind STAT-3, is able to confer a response to IL-10 on a heterologous promoter. These results may be understood in terms of the shared signalling mechanisms of IL-10 and IL-6 and provide evidence of a role for IL-10 in the overexpression of hsp 90 in SLE, with possible pathological consequences. |
| Databáze: | OpenAIRE |
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