BACKGROUND: Interleukin (IL)-12 and IL-18 are major interferon (IFN)-gamma-inducing factors that collaborate with each other. The present study was conducted to determine the distinct roles of IL-12 and IL-18 in the development of dextran sulphate sodium (DSS) colitis in mice. METHODS: Colitis was induced in IL-12p35(-/-), IL-18(-/-), IL-18 receptor(-/-) and control mice with DSS. Clinical and histopathological analysis was conducted using survival rate, weight loss score, diarrhoea score, bloody stool score and histological score. In addition, cytokine production by lamina propria mononuclear cells (LPMCs) was examined using the specific enzyme-linked immunoassay. RESULTS: IL-12p35(-/-) mice developed only a mild disease associated with no lethality and few histopathological abnormalities. In contrast, IL-18(-/-) and IL-18R(-/-) mice developed more severe colitis associated with high lethality and more histopathological abnormalities compared with control mice. LPMCs from DSS-fed IL-18(-/-) mice produced significantly higher amounts of IFN-gamma, while LPMCs from DSS-fed IL-12(-/-) mice produced lower amounts of IFN-gamma and tumour necrosis factor (TNF)-alpha compared with control mice. CONCLUSION: These results suggest that IL-18 might function with manners different from IL-12 at some pathological conditions in the development of colitis.
BACKGROUND: Interleukin (IL)-12 and IL-18 are major interferon (IFN)-gamma-inducing factors that collaborate with each other. The present study was conducted to determine the distinct roles of IL-12 and IL-18 in the development of dextran sulphate sodium (DSS) colitis in mice. METHODS:Colitis was induced in IL-12p35(-/-), IL-18(-/-), IL-18 receptor(-/-) and control mice with DSS. Clinical and histopathological analysis was conducted using survival rate, weight loss score, diarrhoea score, bloody stool score and histological score. In addition, cytokine production by lamina propria mononuclear cells (LPMCs) was examined using the specific enzyme-linked immunoassay. RESULTS:IL-12p35(-/-) mice developed only a mild disease associated with no lethality and few histopathological abnormalities. In contrast, IL-18(-/-) and IL-18R(-/-) mice developed more severe colitis associated with high lethality and more histopathological abnormalities compared with control mice. LPMCs from DSS-fed IL-18(-/-) mice produced significantly higher amounts of IFN-gamma, while LPMCs from DSS-fed IL-12(-/-) mice produced lower amounts of IFN-gamma and tumour necrosis factor (TNF)-alpha compared with control mice. CONCLUSION: These results suggest that IL-18 might function with manners different from IL-12 at some pathological conditions in the development of colitis.
Authors: Roni Nowarski; Ruaidhrí Jackson; Nicola Gagliani; Marcel R de Zoete; Noah W Palm; Will Bailis; Jun Siong Low; Christian C D Harman; Morven Graham; Eran Elinav; Richard A Flavell Journal: Cell Date: 2015-12-03 Impact factor: 41.582
Authors: Hidetoshi Takedatsu; Kathrin S Michelsen; Bo Wei; Carol J Landers; Lisa S Thomas; Deepti Dhall; Jonathan Braun; Stephan R Targan Journal: Gastroenterology Date: 2008-05-07 Impact factor: 22.682
Authors: Nazanin Navabi; Jordan Whitt; Shu-En Wu; Vivienne Woo; Jessica Moncivaiz; Michael B Jordan; Bruce A Vallance; Sing Sing Way; Theresa Alenghat Journal: Cell Rep Date: 2017-05-09 Impact factor: 9.423
Authors: Sergey S Seregin; Natasha Golovchenko; Bryan Schaf; Jiachen Chen; Nicholas A Pudlo; Jonathan Mitchell; Nielson T Baxter; Lili Zhao; Patrick D Schloss; Eric C Martens; Kathryn A Eaton; Grace Y Chen Journal: Cell Rep Date: 2017-04-25 Impact factor: 9.423