Inhibition of Inflammatory Gene Transcription by IL-10 Is Associated with Rapid Suppression of Lipopolysaccharide-Induced Enhancer Activation

Autor(es)

Conaway, Evan A. ; de Oliveira, Dalila C. ; McInnis, Christine M. ; Snapper, Scott B. ; Horwitz, Bruce H.

• Tipo de documento: Artigo Científico
• Fonte: JOURNAL OF IMMUNOLOGY; v. 198, n. 7, p. 2906-2915, APR 1 2017.
• Citações Web of Science: 9

Resumo

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. (AU)

• Processo FAPESP: 15/02610-6 - Avaliação da glutamina como modulatora dos fatores de transcrição NF-kB e c-Rel em macrófagos e linfócitos de camundongos knock out para IL-10 submetidos a restrição alimentar
• Beneficiário: Dalila Cunha de Oliveira
• Modalidade de apoio: Bolsas no Exterior - Estágio de Pesquisa - Doutorado