Amelioration of murine colitis by attenuated Salmonella choleraesuis encoding interleukin-19

Autor: Jian-da Lin, 林建達
Rok vydání: 2007
Druh dokumentu: 學位論文 ; thesis
Popis: 95
Uncontrolled mucosal immunity in the gastrointestinal tract of humans results in chronic inflammatory bowel disease (IBD), such as Crohn’s disease and ulcerative colitis. IBD is a group of chronic disorder that causes inflammation or ulceration in the small and/or large intestines. In previous studies, recombinant interleukin (IL)-10 and genetically modified bacteria secreting IL-10 ameliorated the dextran sulfate sodium (DSS)-induced colitis of IBD model. Recently, human IL-19 has been identified as a member of the IL-10 cytokine family. It influences the maturation of T cells and alters the balance of Th1/Th2 cells in favor of Th2. Furthermore, IL-19 is a transcriptional activator of IL-10 and IL-10 is strongly induced in IL-19-stimulated peripheral blood mononuclear cells. In this study, we investigated whether the expression of murine IL-19 gene was beneficial in ameliorating IBD. Our results showed that the use of the attenuated Salmonella choleraesuis carrying murine IL-19 expressing plasmid for IBD gene therapy reduced the mortality and many clinical markers in DSS- induced acute colitis as compared with those untreated counterparts. We also found that IL-10 was induced in IL-19 treated colitis mice and it prevented the progression at the early stage of DSS-induced colitis. The S. choleraesuis encoding IL-19 for the treatment of IBD provides a new strategy in future clinical application.
Databáze: Networked Digital Library of Theses & Dissertations