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Murine Colitis Modeling using Dextran Sulfate Sodium DSS
Published on: January 19, 2010
Glial cell line-derived neurotrophic factor ameliorates dextran sulfate sodium-induced colitis in mice via a
Jian Zeng1, Huan Yu1, Hua-Tian Gan2
1Department of Gastroenterology and the Center of Inflammatory Bowel Disease, West China Hospital, Sichuan University, Chengdu, Sichuan Province, China.
Abstract:
Glial cell line-derived neurotrophic factor (GDNF) has been reported to protect mice from intestinal inflammation, but its anti-inflammatory mechanisms are poorly understood. Here we found that there was a downregulation in intestinal expression of GDNF accompanied by an increase of M1 macrophages in dextran sulfate sodium (DSS)-induced colitis in mice. GDNF treatment could facilitate the macrophages polarization towards the M2-like phenotype in DSS-treated mice and LPS-stimulated RAW264.7 cells, and reduce pro-inflammatory cytokines and increase anti-inflammatory cytokines. Mechanistically, the activation of PI3K/AKT pathway might contribute to the regulation of GDNF on macrophage phenotypes and inflammatory response. Moreover, the administration of GDNF significantly ameliorated colitis in DSS-treated mice, but this benefit of GDNF was diminished by macrophage depletion. Therefore, we propose a new mechanism whereby GDNF suppresses DSS-induced colitis in mice via a macrophage-mediated pathway.
