| First Author | Conaway EA | Year | 2017 |
| Journal | J Immunol | Volume | 198 |
| Issue | 7 | Pages | 2906-2915 |
| PubMed ID | 28213503 | Mgi Jnum | J:247858 |
| Mgi Id | MGI:5925881 | Doi | 10.4049/jimmunol.1601781 |
| Citation | Conaway EA, et al. (2017) Inhibition of Inflammatory Gene Transcription by IL-10 Is Associated with Rapid Suppression of Lipopolysaccharide-Induced Enhancer Activation. J Immunol 198(7):2906-2915 |
| abstractText | IL-10 limits the magnitude of inflammatory gene expression following microbial stimuli and is essential to prevent inflammatory disease; however, the molecular basis for IL-10-mediated inhibition remains elusive. Using a genome-wide approach, we demonstrate that inhibition of transcription is the primary mechanism for IL-10-mediated suppression in LPS-stimulated macrophages and that inhibited genes can be divided into two clusters. Genes in the first cluster are inhibited only if IL-10 is included early in the course of LPS stimulation and is strongly enriched for IFN-inducible genes. Genes in the second cluster can be rapidly suppressed by IL-10 even after transcription is initiated, and this is associated with suppression of LPS-induced enhancer activation. Interestingly, the ability of IL-10 to rapidly suppress active transcription exhibits a delay following LPS stimulation. Thus, a key pathway for IL-10-mediated suppression involves rapid inhibition of enhancer function during the secondary phase of the response to LPS. |
