Stat3 and C/EBPβ synergize to induce miR-21 and miR-181b expression during sepsis.

ABSTRACT: Myeloid-derived suppressor cells (MDSCs) increase late sepsis immunosuppression and mortality in mice. We reported that microRNA (miR) 21 and miR-181b expression in Gr1⁺CD11b⁺ myeloid progenitors increase septic MDSCs in mice by arresting macrophage and dendritic cell differentiation. Here, we report how sepsis regulates miR-21 and miR-181b transcription. In vivo and in vitro binding studies have shown that C/EBPα transcription factor, which promotes normal myeloid cell differentiation, binds both miRNA promoters in Gr1⁺CD11b⁺ cells from sham mice. In contrast, in sepsis Gr1⁺CD11b⁺ MDSCs miR-21 and miR-181b promoters bind both transcription factors Stat3 and C/EBPβ, which co-imunoprecipitate as a single complex. Mechanistica

SUBMITTER: McClure C 

PROVIDER: S-EPMC5209283 | biostudies-literature | 2017 Jan

REPOSITORIES: biostudies-literature