Journal of Clinical and Cellular Immunology
Open Access
ISSN: 2155-9899
ISSN: 2155-9899
Department of Internal Medicine, Wake Forest University School of Medicine, Winston-Salem, United States of America
Research Article
Nuclear S100A9 protein induces anti-inflammatory gene expression in sepsis
Author(s): Isatou Bah, Dima Youssef, Mary E. Howell, Zhi Q. Yao, Charles E. McCall and Mohamed El Gazzar*
Expansion and accumulation of Myeloid-Derived Suppressor Cells (MDSCs) during sepsis contribute to post-sepsis immunosuppression, as these cells suppress innate and adaptive immunity. We have shown that the proinflammatory S100A9 protein accumulates in the nucleus of MDSCs during late sepsis in both mice and humans. In this context, nuclear S100A9 acts as a transcription co-factor to induce the expression of two potent immunosuppressive cytokines, Interleukin-10 (IL-10) and Transforming Growth Factor-β (TGF-β). S100A9 knockdown in MDSCs from late septic mice and late septic patients significantly reduced IL-10 and TGF-β production upon ex vivo stimulation with bacterial lipopolysaccharide. In contrast, ectopic expression of S100A9 in MDSCs from S100A9-deficient mice significantly increased IL-10 and TGF-β production. Chromatin immunoprecipitation revealed that S100.. View More»
DOI:
10.35248/2155-9899.25.16.749