Glial cell line-derived neurotrophic factor ameliorates dextran sulfate sodium-induced colitis in mice via a macrophage-mediated pathway

Int Immunopharmacol. 2021 Sep 17;100:108143. doi: 10.1016/j.intimp.2021.108143. Online ahead of print.ABSTRACTGlial 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.PMID:34543979 | DOI:10.1016/j.intimp.2021.108143
Source: International Immunopharmacology - Category: Allergy & Immunology Authors: Source Type: research