Title

Anti-IL-6 siRNA Therapy Increases Immunosuppressive Cytokine Expression in Human Dendritic Cells

Publication Year

2011

Keywords

T lymphocytes, cytokine, Th17, siRNA, RNA interference, interventional therapy, diabetes

Disciplines

Biology | Cell and Developmental Biology | Preventive Medicine

Abstract

Recent experiments have demonstrated that Th17 lymphocytes secrete the inflammatory cytokine IL-17 and are important in the initiation of type 1 diabetes onset in non-obese diabetic mice. Correlative studies in type 1 diabetic patients confirm that Th17 lymphocyte populations increase during diabetes onset. Cytokine secretion studies in non-obese diabetic cells suppressed differentiation of Th17 cells and induced regulatory T cell proliferation responsible for suppression of dendritic cells induced islet beta cell inflammation. Based on these observations, an anti-IL-6 siRNA interventional therapeutic strategy was designed to test the hypothesis that blockage of IL-6 expression in human dendritic cells could inhibit IL-6 biosynthesis and suppress the TH17 lymphocyte development responsible for early stages of diabetes onset. Interleukin-6 siRNA was delivered by liposomal transfection to human umbilical cord-derived immature dendritic cells previously activated with E. coli lipopolysaccharide. Reductions in IL-6 mRNA biosynthesis in siRNA inoculated dendritic cells were examined initially by reverse transcriptase synthesis of cDNAs followed by PCR amplification and electrophoretic detection of qualitative IL-6 mRNA levels. Changes in the level of dendritic cell-secretion of IL-6 protein in the cultured medium were qualified by enzyme-linked immunosorbent assay. As a result, expression of IL-1B, TNF-a, IL-10, and TGF-B was increased in the transfected dendritic cells.

Department 1 Awarding Honors Status

Biology

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