Therapeutic Effect of Interleukin-23 p19 RNA Interference in Mice With Experimental Colitis
10.3969/j.issn.1008-7125.2019.01.003
- Author:
Yutang REN
1
Author Information
1. Institute for Immunology, School of Medicine, Tsinghua University
- Publication Type:Journal Article
- Keywords:
Inflammatory Bowel Disease;
Interleukin-23;
RNA Interference;
Th17 Cells
- From:
Chinese Journal of Gastroenterology
2019;24(1):10-16
- CountryChina
- Language:Chinese
-
Abstract:
Background: Inflammatory bowel disease (IBD) is an autoimmune bowel disease with poor clinical outcome. Proinflammatory cytokines are the main targets of biological therapies. Interleukin-23 (IL-23) is a key factor in IBD pathogenesis. Monoclonal antibodies against subunit of IL-23 have been reported to have therapeutic effects. Aims: To investigate the therapeutic effect of IL-23 RNA interference in mice with experimental colitis and the underlying mechanism. Methods: 2,4,6-trinitrobenzenesulfonic acid (TNBS) enema was used to induce experimental colitis in mice, which were then injected with IL-23 p19 shRNA lentivirus or control shRNA lentivirus through caudal vein. Mice without lentivirus injection were served as model controls. After 2 weeks, disease activity index and histopathological inflammatory score, serum and colon tissue IL-23, IL-17 and tumor necrosis factor-α (TNF-α) expressions, as well as colon tissue Th17 cells were detected and compared. Results: IL-23 p19 shRNA therapy significantly reduced disease activity index and histopathological inflammatory score in mice with experimental colitis (P<0.05). By inhibiting IL-23 expression, IL-23 p19 shRNA suppressed further the colon tissue Th17 cells and subsequently reduced systemic and colon tissue IL-17 and TNF-α expressions significantly (P<0.05). Conclusions: IL-23 RNA interference has therapeutic effect in mice with experimental colitis. The mechanism lies in suppression of Th17 cells and its effector cytokine IL-17.
