IL-10 induces IL-10 in primary human monocyte-derived macrophages via the transcription factor Stat3
| Autor: | Bernard Burke, Timothy Smallie, Lynn M. Williams, Brian M. J. Foxwell, Loems Ziegler-Heitbrock, Andrew D. Foey, Karl J. Staples |
|---|---|
| Rok vydání: | 2007 |
| Předmět: |
Lipopolysaccharides
STAT3 Transcription Factor Messenger RNA medicine.medical_treatment Macrophages Immunology RNA Biology Molecular biology stat Monocytes Adenoviridae Interleukin-10 Interleukin 10 Cytokine medicine biology.protein Immunology and Allergy Humans RNA Messenger Autocrine signalling STAT3 Promoter Regions Genetic Transcription factor |
| Zdroj: | Journal of immunology (Baltimore, Md. : 1950). 178(8) |
| ISSN: | 0022-1767 |
| Popis: | IL-10 is an important immunosuppressive cytokine that can down-regulate expression of other cytokines and has been shown to down-regulate itself. We show, in this study, that treatment of human monocyte-derived macrophages with IL-10 induces IL-10 mRNA in a dose- and time-dependent manner with an optimum induction at 100 ng/ml and at 6 h, whereas IL-10-induced IL-10 protein can be detected at 18 h. In the same cells, IL-10 can partially suppress IL-10 mRNA induced by LPS, but only down to the level of IL-10-induced IL-10. An adenoviral luciferase reporter construct driven by the −195 IL-10 promoter, which contains a Stat motif, was readily induced by both IL-10 and LPS. Mutation of this Stat motif ablated IL-10 activation of this promoter, but not the LPS activation. Finally, we show that overexpression of a dominant-negative Stat3 protein will prevent IL-10 induction, but not LPS induction, of IL-10 mRNA. These data show that IL-10 induces IL-10 in monocyte-derived macrophages in an autocrine manner via activation of the transcription factor Stat3. |
| Databáze: | OpenAIRE |
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