IL-10 induces IL-10 in primary human monocyte-derived macrophages via the transcription factor Stat3

Staples, K.J., Smallie, T., Williams, L.M., Foey, A., Burke, B., Foxwell, B.M.J. and Ziegler-Heitbrock, L. (2007) IL-10 induces IL-10 in primary human monocyte-derived macrophages via the transcription factor Stat3. Journal of Immunology, 178 (8), 4779-4785. (doi:10.4049/?jimmunol.178.8.4779). (PMID:17404258)

Abstract

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

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Contributors

Author: K.J. Staples

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