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J. Gastroenterol. Hepatol. · Dec 2020
Oligosaccharide-dependent anti-inflammatory role of galectin-1 for macrophages in ulcerative colitis.
- Shuko Iwatani, Shinichiro Shinzaki, Takahiro Amano, Yuriko Otake, Mizuki Tani, Takeo Yoshihara, Yoshiki Tsujii, Yoshito Hayashi, Takahiro Inoue, Daisuke Okuzaki, Tsunekazu Mizushima, Eiji Miyoshi, Hideki Iijima, and Tetsuo Takehara.
- Department of Gastroenterology and Hepatology, Graduate School of Medicine, Osaka University, Suita, Japan.
- J. Gastroenterol. Hepatol. 2020 Dec 1; 35 (12): 2158-2169.
Background And AimGalectin-1 plays a protective role against colitis by binding with polylactosamine structures on macrophages in β-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.MethodsThe 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) 2-/- mice, 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.ResultsIn ulcerative colitis patients, tissue expression of galectin-1was decreased in inflamed mucosa compared with non-inflamed mucosa. Galectin-1 induced interleukin-10 production in BMDMs, and the interleukin-10 production was abrogated by lactose, which inhibits the interaction of oligosaccharide-galectin binding. Dextran sodium sulfate colitis was significantly ameliorated in Rag2-/- mice 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 protein β and CD163, but decreased the expression of CD80 on BMDMs.ConclusionGalectin-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.© 2020 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.
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