Project description:Anti-proinflammatory cytokine therapies against interleukin (IL)-6 and tumor necrosis factor (TNF)-a are major advances in treating inflammatory diseases. We found that 2-deoxy-D-glucose (2-DG), a simple monosaccharide, attenuated IL-6 responses by inhibiting N-linked glycosylation of the IL-6 receptor gp130. Aglyco forms of gp130 failed to bind IL-6 and to activate downstream signals. 2-DG completely inhibited dextran sodium sulfate-induced inflammatory bowel disease that was partially dependent on IL-6.
Project description:Compromise of the intestinal barrier have been associated with a series of inflammatory conditions where the routine controls nutrient absorption and pathogens exclusion is lost to different degrees. The intestinal epithelial cells form a barrier of selective permeability which protects from invasion by the normal bacteria present in the gut. When the barrier is compromised, bacteria and their products can attack the cells and cause inflammation, which can (in severe cases) cause sepsis. Mesenteric lymph nodes play a crucial role in the immune response and are of particular importance in the study of Inflammatory Bowel Disease (IBD) patients due to their involvement in the disease process. To assess the efficiency of gut immune barrier, we collected the pre-nodal lymph from Inflammatory Bowel Disease (IBD) subjects and performed a comprehensive proteomic analysis. The current study is complementary extension of the proteomics signature found in DSS-induced colitis mouse model, providing an insight in the lymph composition, and associated biochemical changes, in the set of samples (n=6) recruited from the Inflammatory Bowel Disease (IBD), subjects undergoing intestinal resection. Following bottom-up analysis, the enrichment analysis – GO and Ingenuity pathway analysis (IPA) analysis identified several pathways pointing towards a damaging phenotype.
Project description:Expression profiling of human colon mucosa samples aquired from inflammatory bowel disease patients and healthy controls. Expression profiling was done using Illumina Human HT-12 arrays, and data analysis was performed using tools from the Bioconductor package
Project description:Inflammatory bowel disease (IBD) is a multiple-genes-involved chronic disease and current available targeted drugs for IBD only deliver moderate efficacy. Whether there is a single gene that systematically regulates IBD is not yet known. Here we showed that the expression of miR-146a in colon was elevated in Dextran Sulfate Sodium Salt (DSS)-induced IBD mice and patients with IBD. DSS induced dramatic body weight loss and much more rectal bleeding, shorter colon length and colitis in miR-146a knock-out mice than wild type (WT) mice. The miR-146a mimics alleviated DSS-induced symptoms in both DSS-induced miR-146a-/- and WT mice. Further RNA sequencing illustrated that deficiency of miR-146a de-repressed majority of DSS-induced IBD-related genes which cover multiple genetic regulatory networks in IBD, and supplement of miR-146a mimics inhibited expression of many IBD-related genes. DOI 10.3389/fimmu.2024.1366319
Project description:A compromised pathology of the intestinal barrier have been associated with a series of inflammatory conditions where the routine controls nutrient absorption and pathogens exclusion is lost to different degrees. When the epithelial barrier is compromised, bacteria and their products can attack the cells and cause inflammation, sometime leading to sepsis. Studying the lymph peptidome in inflammatory bowel disease (IBD) can offer valuable insights into the underlying mechanisms, disease progression, and potential therapeutic targets. To assess the efficiency of gut immune barrier, we collected the pre-nodal lymph from Inflammatory Bowel Disease (IBD) subjects and performed a comprehensive peptidomic analysis. . The current study is complementary extension of the proteomics signature found in DSS-induced colitis mouse model, providing an insight in the lymph composition inclined to an inflammatory phenotype which was also mirrored by a unique set of peptidome/degradome. Furthermore, the identified peptides mapped to a wide range of intracellular and extracellular pathways, encompassing cellular stress, apoptosis, and extracellular matrix degradation related pathways. A significant fraction of peptides was also found to be derived from bacterial origin with a predicted binding affinity to different MHC I and MHC II human haplotypes.
Project description:Thrombospondin 1 (TSP-1) is an anti-angiogenic matricellular protein with regulatory functions in inflammation and cancer. The type 1 repeats (TSR) domains of TSP-1 have been shown to interact with a wide range of proteins that result in the anti-angiogenic and anti-tumor properties of TSP-1. To evaluate potential therapeutic effects of TSRs in inflammatory bowel disease, we conducted clinical, histological and gene microarray analyses on a mouse model of induced colitis. We used Affymetrix GeneChips to determine the changes in the genetic profile underlying TSR-treatment coincident with induction of colitis using DSS. We identified differentially expressed genes among the treatment groups. Using DSS (dextran sulfate sodium) to induce colitis, wild-type mice were simultaneously injected with either saline or one form of TSP-1 derived peptides, containing either the three domains of the TSR (3TSR), the two last domains (TSR2), or TSR2 with the RFK sequence (TSR2+RFK). Wt mice drinking water only was used as reference.
Project description:Our previous study demonstrated that Galectin-1 plays a protective role for colitis by binding with polylactosamine structures in β-1,4-galactosyltransferase I-deficient mice, but precise function of galectin-1 remains unknown. In the present study, we investigated about the anti-inflammatory role of galectin-1 for macrophages to ameliorate inflammatory bowel disease in both animal model and human tissue sample. To know the anti-inflammatory effect of galectin-1 in vivo, transfer of BMDMs cultured with galectin-1 into Recombination activating gene (Rag) 2-/- mice and treatment with galectin-1 in dextran sodium sulfate (DSS) colitis model were performed. Furthermore, RNA sequencing was performed to know the character of macrophages treated with galectin-1. In UC patients, tissue expressions of galectin-1 were decreased in inflamed mucosa compared with those in non-inflamed mucosa. Galectin-1 induced IL-10 production in BMDMs, and the production was abrogated by the addition of lactose, which inhibits the interaction of oligosaccharide-galectin binding. DSS colitis was significantly ameliorated in Rag2-/- mice to which galectin-1-treated BMDMs were transferred, than those transferred with vehicle-treated BMDMs. RNA sequence showed that treatment with Galectin-1 increased the expression of CCAAT/enhancer binding protein β and CD163 but decreased CD80 on BMDMs. Galectin-1 ameliorates murine colitis through the induction of oligosaccharide-dependent anti-inflammatory properties to macrophages.