Abstract
DSS induced colitis is a chronic inflammatory disease characterized by inflammation in the gastrointestinal tract, which destabilizes the gut and induces an uncontrolled immune response. Although DSS induced colitis is generally thought to develop as a result of an abnormally active intestinal immune system, its pathogenesis remains unclear. Gene associated with retinoid interferon induced mortality (Grim) 19 is an endogenous specific inhibitor of STAT3, which regulates the expression of proinflammatory cytokines. In this study, we investigated the influence of GRIM19 in a DSS induced colitis mouse model. We hypothesized that Grim19 would ameliorate DSS induced colitis by altering STAT3 activity and intestinal inflammation. Grim19 ameliorated DSS induced colitis severity and protected intestinal tissue. The expression of STAT3 and proinflammatory cytokines such as IL-1β and TNF-α in colon and lymph nodes was decreased significantly by Grim19. Moreover, DSS induced colitis progression in a Grim19 transgenic mouse line was inhibited in association with a reduction in STAT3 and IL-17 expression. These results suggest that Grim19 attenuates DSS induced colitis by suppressing the excessive inflammatory response mediated by STAT3 activation.
Highlights
dextran sulfate sodium (DSS) induced colitis is a chronic inflammatory disease characterized by dysregulated immune responses in the gastrointestinal tract
The IL-1β, -6, -8, -17 and TNF-α protein levels were downregulated significantly in DSS induced colitis mice treated with Grim19 compared with control mice (Fig 2A)
Grim19 expression was increased significantly, whereas STAT3 production was reduced significantly, in DSS induced colitis mice treated with Grim19 compared with control mice (Fig 3A)
Summary
DSS induced colitis is a chronic inflammatory disease characterized by dysregulated immune responses in the gastrointestinal tract. DSS induced colitis is an autoimmune disease characterized by chronic and relapsing inflammatory responses in the gastrointestinal tract. As the gastrointestinal tract plays an essential role in the modulation of the immune response to pathogens, unintended weight loss and rectal bleeding [1] make DSS induced colitis a severe inflammatory disorder. To treat DSS induced colitis, downregulation of proinflammatory cytokines, including interleukin (IL)-17, is an important approach [2, 3].
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