Year: 2020
Type: article
Abstract: Non-steroidal anti-inflammatory drugs (NSAIDs) induce ulcers in the gastrointestinal tract, including the stomach and small intestine. NSAID-induced gastric ulcers can be prevented by taking acid-neutralizing/inhibitory drugs and cytoprotective agents. In contrast, there are no medicines to control NSAID-induced small intestinal ulcers, which are accompanied by a mucosal invasion of bacteria and subsequent activation of immune cells. Galectin-3 (Gal3), an endogenous lectin, has anti-microbial and pro-inflammatory functions. In the small intestine, since Gal3 is highly expressed in epithelial cells constitutively and macrophages inducibly, the Gal3 level can affect microbiota composition and macrophage activation. We hypothesized that the modulation of Gal3 expression could be beneficial in NSAID-induced intestinal ulcers. Using Gal3 knockout (Gal3KO) mice, we determined whether Gal3 could be a therapeutic target in NSAID-induced intestinal ulcers. Following the administration of indomethacin, an NSAID, we found that small intestinal ulcers were less severe in Gal3KO mice than in wild-type (WT) mice. We also found that the composition of intestinal microbiota was different between WT and Gal3KO mice and that bactericidal antibiotic polymyxin B treatment significantly suppressed NSAID-induced ulcers. Furthermore, clodronate, a macrophage modulator, attenuated NSAID-induced ulcers. Therefore, Gal3 could be an exacerbating factor in NSAID-induced intestinal ulcers by affecting the intestinal microbiota population and macrophage activity. Inhibition of Gal3 may be a therapeutic strategy in NSAID-induced intestinal ulcers. Clinical Trial Registration: www.ClinicalTrials.gov, identifier NCT03832946.
Source: Frontiers in Immunology
Language: English
Topic: Galectins and Cancer Biology
Subfield: Immunology
Field: Immunology and Microbiology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $2,950
Awards: G2112963525, COBRE Center for Molecular and Tumor Virology, Elucidation of the pathogenesis of chronic inflammatory neurological diseases from the perspective of chronic infection with Helicobacter pylori, Interactions between Th17 and CD8+ T cells in animal models of multiple sclerosis, Role of galectin-3 and intestinal bacteria flora on NSAID-induced small intestinal ulcer, Bioinformatics analyses for identification of molecules which contribute to prognosis and treatment in viral myocarditis, Significance of B7 family expressed on macrophages relevant to radiation necrosis of brain, Virus infection induces neuroinflammation by autoimmune T cells in the multiple sclerosis model, Identification of biomarkers in animal models of progressive multiple sclerosis using RNA sequencing
OpenAlex ID: W3087858135