Dimethyl itaconate alleviates Escherichia coli-induced endometritis by activating the guanosine-CXCL14 axis via increasing the abundance of Muribaculaceae
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ABSTRACT:
PROVIDER: PRJNA1141976 | ENA |
REPOSITORIES: ENA
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Project description:Endometritis, a prevalent reproductive system disease with high incidence, leads to reproductive dysfunction and potential miscarriage in both humans and animals, impacting human health and the dairy industry, resulting in significant economic loss. Gut microbiota plays an important role in the pathogenesis of endometritis. However, the specific microbial and metabolic mediators participating in the pathogenesis remain to be identified. In this study, we found that the concentration of itaconate in the feces of mice increased after endometritis induced by Escherichia coli (E. coli) infection, suggesting a potential association between itaconate and inflammatory processes. Here, we investigated the specific role of dimethyl itaconate (DI), a derivative of itaconate with potent anti-inflammatory and immunomodulatory properties on endometritis. Oral administration of DI ameliorated the symptoms of E. coli-induced endometritis in mice. The protective effect was abolished by antibiotic-induced depletion of the gut microbiota, and fecal microbiota transplantation (FMT) from DI-treated mice to recipient mice ameliorated E. coli-induced endometritis. Integrative multiomics revealed that the addition of DI led to an enrichment of Muribaculaceae and the microbial purine metabolite guanosine in the feces. Muribaculum intestinale (DSM 28989), a bacterium of Muribaculaceae or guanosine supplementation alleviated E. coli-induced endometritis in mice. Mechanistically, DI promoted the multiplication of Muribaculaceae, and supplementation of M. intestinale upregulated the level of guanosine in the uterus. Transcriptome data and antibody-neutralizing experiment demonstrated the protective effect of guanosine in E. coli-induced endometritis was mediated by activating the expression of CXCL14 in uterine epithelial cells. In conclusion, our study elucidates the significant role of the gut microbiota and its metabolites in safeguarding the uterus against pathogen infections, providing substantiation for the regulation of distal organ by the gut microbiota, and establishing a basis for preventive measures against related diseases through the gut-X axis.
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Project description:Monocytic leukemia cell line, THP-1 cells are known to respond to CXCL14. To identfy transcriptional regulation of CXCL14 signalling, we analyse gene expression changed with CXCL14 treatment. THP-1 treated with CXCL14 or PBS treated sample were used.
2013-12-17 | E-GEOD-44550 | biostudies-arrayexpress
Project description:Monocytic leukemia cell line, THP-1 cells are known to respond to CXCL14. To identfy transcriptional regulation of CXCL14 signalling, we analyse gene expression changed with CXCL14 treatment.
2013-12-17 | GSE44550 | GEO
Project description:Background：The widespread silencing of CXCL14 in advanced colon cancer underscores the association between CXCL14 and the development of colon cancer. Some studies have demonstrated in vitro that CXCL14 can inhibit the growth and metastasis of colon cancer cell, and it has also been studied in other disease models for its regulation of immune cell infiltration. Aims: The aim of this study is to clarify the transcriptional regulation of colon cancer cells mediated by CXCL14 and its regulatory role in the tumor microenvironment. Method：We analyzed the expression characteristics of CXCL14 in clinical databases of colon cancer. CXCL14 overexpression cell lines were established to study its functions on gene transcriptional regulation and cell physiology. Through subcutaneous tumor models, we investigated the effects of CXCL14 on the immune microenvironment. Result：Firstly, the clinical data revealed that CXCL14 is silenced during cancer progression, and negatively associated with EMT and cell proliferation markers, and positively associated with the abundance of T cells and NK cells in colon tissue. Secondly, RNA-seq reveals that CXCL14 overexpression is negatively associated with cell EMT, and inhibits tumor migration and invasion. Western blot (WB) assay confirmed that CXCL14 inhibits the Erk/MAPK and Akt signaling pathways. Finally, subcutaneous tumor models demonstrate that CXCL14 overexpression inhibited tumor growth, increased the infiltration of tumor-associated T cells and DC cells, activated the anti-tumor immune response, antigen processing and presentation, and T helper differentiation in the tumor microenvironment. Conclusion：CXCL14 becomes silenced in late-stage colon cancer samples. In vivo and in vitro experiments demonstrate that CXCL14 inhibits tumor EMT, proliferation, and metastasis through autocrine signaling. It also enhances the infiltration of T and NK lymphocytes through paracrine signaling and inhibits the proliferation of subcutaneous tumors.
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Project description:Cxcl14+/- mice were mated with Cxcl14+/- mice, the embryos of pregnant females were collected on E13.5. After genotyping, the maternal part and fetal part of Cxcl14-/- and Cxcl14+/+ placentas were dissect out to extract total RNA respectively (n = 3). Total RNA was extracted using PureYield™ RNA Midiprep System (Promega).The maternal part of placenta that contained mesometrial lymphoid aggregate of pregnancy (MLAp) and decidua basalis (DB); the fetal part ofplacenta consisted of spongiotrophoblast and labyrinthin layer.Microarray hybridization was performed using a Mouse NimbleGen cDNA Microarray Kit (Roche), at CapitalBio Co., Ltd.(Beijing,China). Primary data were scaned using NimbleGen MS200 (Roche), and then extracted using NimbleScan system (Roche). Cxcl14+/- mice were mated with Cxcl14+/- mice, the embryos of pregnant females were collected on E13.5. After genotyping, the maternal part and fetal part of Cxcl14-/- and Cxcl14+/+ placentas were dissect out to extract total RNA respectively (n = 3). Total RNA was extracted using PureYield™ RNA Midiprep System (Promega).The maternal part of placenta that contained mesometrial lymphoid aggregate of pregnancy (MLAp) and decidua basalis (DB); the fetal part ofplacenta consisted of spongiotrophoblast and labyrinthin layer.Microarray hybridization was performed using a Mouse NimbleGen cDNA Microarray Kit (Roche), at CapitalBio Co., Ltd.(Beijing,China). Primary data were scaned using NimbleGen MS200 (Roche), and then extracted using NimbleScan system (Roche).
2013-06-19 | E-GEOD-48095 | biostudies-arrayexpress
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