Shaping Gene Expression in Activated and Resting Primary Macrophages by IL-10

Abstract

IL-10 regulates inflammation by reducing cytokine and chemokine production from activated macrophages. We performed microarray experiments to identify possible effector molecules of IL-10 and to investigate the global effect of IL-10 on the transcriptional response induced in LPS-activated macrophages. To exclude background effects of endogenous IL-10, macrophages from IL-10-deficient mice were used. IL-10 up-regulated expression of a small number of genes (26 and 37 after 45 min and 3 h, respectively), including newly identified and previously documented targets such as suppressor of cytokine signaling-3 and IL-1 receptor antagonist. However, the activation program triggered by LPS was profoundly affected by IL-10. IL-10 repressed 62 and further increased 15 of 259 LPS-induced genes. For all genes examined, the effects of IL-10 were determined to be STAT3-dependent. These results suggest that IL-10 regulates STAT3-dependent pathways that selectively target a broad component of LPS-induced genes at the mRNA level.

Expression profiling of IL‐10‐regulated genes in human monocytes and peripheral blood mononuclear cells from psoriatic patients during IL‐10 therapy

“…Although we have found far more IL-10-regulated genes, probably due to the different methodical approaches, we confirmed 18 out of 19 IL-10-regulated genes in human monocytes published by Williams et al (see supplementary data at http://www.charite.de/immunologie/IL-10 genes). Furthermore, most of the genes regulated by IL-10 in murine macrophages [31] could be confirmed by our in vitro study on human monocytes.…”

“…This is particularly true for the immunosuppressive effects by IL-10 on the LPSinduced pro-inflammatory response, which was one major focus of research interest in the past. Therefore we and others [31,32] tried to approach to this question by identifying genes which are regulated by IL-10 with the means of microarray gene profiling. For the first time, we show a comprehensive overview of genes regulated by IL-10 in human immune cells not only in vitro but also in vivo.…”

“…Two very recent studies by Lang et al [31] and Williams et al [32] have analyzed IL-10-induced genes in mouse macrophages and human monocytes, respectively. However, their interesting studies differ in various aspects from ours.…”

Adult behavioral and pharmacological dysfunctions following disruption of the fetal brain balance between pro-inflammatory and IL-10-mediated anti-inflammatory signaling

“…This antiinflammatory effect is likely to be accounted for by the capacity of IL-10 to selectively suppress pro-inflammatory gene transcription in activated macrophages. 38 In addition, the macrophage-specific overexpression of IL-10 also abolished the fetal brain TNF-a response to maternal immunological stimulation. TNF-a is known to have potent neurodevelopmental effects by inhibiting neuronal cell survival 11 and cortical dendrite development 12 and synergistic interactions exist between TNF-a and other proinflammatory cytokines in these processes.…”

Human adipose tissue macrophages are of an anti-inflammatory phenotype but capable of excessive pro-inflammatory mediator production

“…As a secondary outcome of this study, human M2 macrophages were for the first time thoroughly analyzed regarding surface protein expression thus corroborating other studies mainly investigating gene expression and/or murine cells. 11,12,16,29,30 Surface marker characteristics of ATMs are important not only for their quantification but also for their isolation to be used in in vitro experiments, for example, to investigate the cellular source of adipokines and chemokines. 27,31 So far, only CD31 and CD45 have been shown to be expressed on the surface of human CD14 pos cells derived from the AT.…”