Oligosaccharide-dependent anti-inflammatory role of galectin-1 for macrophages in ulcerative colitis.
J Gastroenterol Hepatol. 2020 May 18. Epub 2020 May 18. PMID: 32424849
BACKGROUND: Galectin-1 plays a protective role against colitis by binding with polylactosamine structures on macrophages inβ-1,4-galactosyltransferase I-deficient mice, but the precise function of galectin-1 remains unknown. In the present study, we investigated the anti-inflammatory role of galectin-1 on macrophages to ameliorate ulcerative colitis in both animal model and human tissue samples.
METHODS: The expression of galectin-1 in colonic tissues of ulcerative colitis patients was evaluated by immunohistochemistry. Cytokine production of mouse bone marrow-derived macrophages (BMDMs) cultured with galectin-1 was investigated. Galectin-1 binding capacity and polylactosamine expression in macrophages stimulated with lipopolysaccharides were evaluated by flow cytometry. BMDMs cultured with galectin-1 were transferred into Recombination activating gene (Rag) 2mice and the severity of the dextran sodium sulfate-induced colitis model was investigated. Furthermore, RNA sequencing was performed to characterize macrophages treated with galectin-1.
RESULTS: In ulcerative colitis patients, tissue expression of galectin-1was decreased in inflamed mucosa compared with non-inflamed mucosa. Galectin-1 induced interleukin (IL)-10 production in BMDMs, and the IL-10 production was abrogated by lactose, which inhibits the interaction of oligosaccharide-galectin binding. Dextran sodium sulfate colitis was significantly ameliorated in Rag2mice undergoing galectin-1-treated BMDM transfer compared with those undergoing vehicle-treated BMDM transfer. RNA sequencing revealed that treatment with galectin-1 increased the expression of CCAAT/enhancer binding proteinβ and CD163, but decreased the expression of CD80 on BMDMs.
CONCLUSION: Galectin-1, whose expression is decreased in the inflamed mucosa of ulcerative colitis patients, can ameliorate murine colitis by conferring oligosaccharide-dependent anti-inflammatory properties to macrophages.