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Title

Genomic analysis of LPS-stimulated myeloid cells identifies a common pro-inflammatory response but divergent IL-10 anti-inflammatory responses

AuthorsHutchins, Andrew Paul; Takahashi, Yoshiko; Miranda-Saavedra, Diego
Issue Date13-Mar-2015
PublisherNature Publishing Group
CitationScientific Reports 5: 9100 (2015)
AbstractInflammation is an essential physiological response to infection and injury that must be kept within strict bounds. The IL-10/STAT3 anti-inflammatory response (AIR) is indispensable for controlling the extent of inflammation, although the complete mechanisms downstream of STAT3 have not yet been elucidated. The AIR is widely known to extend to other myeloid cells, but it has best been characterized in macrophages. Here we set out to characterize the LPS-mediated pro-inflammatory response and the AIR across a range of myeloid cells. We found that whereas the LPS-induced pro-inflammatory response is broadly similar among macrophages, dendritic cells, neutrophils, mast cells and eosinophils, the AIR is drastically different across all myeloid cell types that respond to IL-10 (all bar eosinophils). We propose a model whereby the IL-10/STAT3 AIR works by selectively inhibiting specific pathways in distinct cell types: in macrophages the AIR most likely works through the inhibition of NF-κB target genes; in DCs and mast cells through indirect IRF disruption; and in neutrophils through IRF disruption and possibly also indirect NF-κB inhibition. In summary, no conserved IL-10/STAT3 AIR effectors were identified; instead a cell type-specific model of the AIR is proposed.
URIhttp://hdl.handle.net/10261/124378
DOI10.1038/srep09100
Identifiersdoi: 10.1038/srep09100
issn: 2045-2322
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