IL-10 induces IL-10 in primary human monocyte-derived macrophages via the transcription factor Stat3.
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.
Staples
Karl J
KJ
Department of Infection, Immunity and Inflammation, University of Leicester, Leicester, UK.
Smallie
Timothy
T
Williams
Lynn M
LM
Foey
Andy
A
Burke
Bernie
B
Foxwell
Brian M J
BM
Ziegler-Heitbrock
Loems
L
D000256:Adenoviridae / Q000235:genetics; D006801:Humans; D016753:Interleukin-10 / Q000235:genetics / Q000494:pharmacology*; D008070:Lipopolysaccharides / Q000494:pharmacology; D008264:Macrophages / Q000276:immunology* / Q000378:metabolism; D009000:Monocytes / Q000166:cytology*; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000032:analysis; D050796:STAT3 Transcription Factor / Q000502:physiology*
D008070:Lipopolysaccharides; D012333:RNA, Messenger; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; D016753:Interleukin-10