Large-Scale Integrative Analysis of Epigenetic Modifications Induced by Isotretinoin, Doxycycline and Metronidazole in Murine Colonic Intestinal Epithelial Cells
نویسندگان
چکیده
Environmental factors are playing a central role in triggering inflammatory responses in the intestine. There is increasing evidence that the development of inflammatory bowel disease (IBD) is deriving from an aberrant immune response to the commensal gut microbiota triggered by various environmental factors in a susceptible host. A vitamin A derivate used in acne therapy (isotretinoin) has been inconsistently associated with the onset of IBD. However, what needs to be considered is the previous treatment of acne patients with antibiotics that are also associated with the development of IBD, thus representing a crucial confounding factor. Here, we studied whether doxycycline (acne therapy), metronidazole (IBD therapy) or isotretinoin are able to induce alterations in DNA methylation and microRNA expression patterns in murine colonic intestinal epithelial cells (IECs). Additionally, we analyzed time-dependent changes in the aforementioned epigenetic mechanisms to study how epigenetic signatures evolve over time. As for changes in DNA methylation, we found isotretinoin to have strong demethylating effects, while antibiotic treatment had only a moderate impact. Isotretinoin-mediated demethylation resolved after a washout phase, not supporting an association between isotretinoin treatment and IBD. Regarding microRNA and mRNA expression, isotretinoin and doxycycline, but not metronidazole, potentially induce long-term changes in microRNA/mRNA expression profiles towards the down-regulation of immune responses. Analysis of time-dependent DNA methylation showed stable marks over a time frame of 4 weeks. Furthermore, novel microRNAs were identified (e.g., microRNA-877-3p), which might be of relevance in IEC development.
منابع مشابه
Doxycycline, metronidazole and isotretinoin: Do they modify microRNA/mRNA expression profiles and function in murine T-cells?
Inflammatory bowel disease (IBD) may develop due to an inflammatory response to commensal gut microbiota triggered by environmental factors in a genetically susceptible host. Isotretinoin (acne therapy) has been inconsistently associated with IBD onset and flares but prior treatment with antibiotics, also associated with IBD development, complicates the confirmation of this association. Here we...
متن کاملEffects of Yacon on Colonic IFN-γ and Goblet Cells of 2,4,6-Trinitrobenzene Sulfonic Acid-Induced Colitis Mouse Model
Background: IBD is a chronic inflammatory condition associated with damage to the intestinal mucosal barrier. Supplementation of yacon tubers has been known to give positive effect in intestinal health. Therefore, we conducted the study to investigate the effect of yacon tuber powder on Th1 activation pathway by evaluating IFN-γ levels and the number of goblet cells in the colon of colitis mous...
متن کاملEpigenetic Modifications of Host Genes Induced by Bacterial Infection
Introduction: Epigenetic mechanisms regulate expression of the genome to generate various cell types during development or coordinate cellular responses to external stimulus. While epigenetics is of fundamental importance in eukaryotes, it plays a different role in bacteria. This article uncovers the most important recent data on how bacteria can alter epigenetic marks and can also contribute t...
متن کاملSalidroside regulates the expressions of IL-6 and defensins in LPS-activated intestinal epithelial cells through NF-κB/MAPK and STAT3 pathways
Objective(s): To reveal the detailed mechanism underlying the functions of salidroside on the inflammation of intestinal epithelial cells during IBD.Materials and Methods: Quantitative real-time PCR was employed to assess the expression of IL-6, IL-10, and α-defensins 5 and 6. ELISA assay was performed to measure the secretion of IL-6 and IL-10. MTT assay was used to determine the cell viabilit...
متن کاملP-88: Comparing Epigenetic Profile of Oct4 Regulatory Region in Embryonal Carcinoma Cells under Retinoic Acid Induction
Background: Embryonal carcinoma (EC) cells derived from germ cell tumors are valuable tools for investigating differentiation and developmental biology processes in vitro. The advantage of the reproducible and rapid expansion of these cell lines provides a useful alternative to embryos for the study of mammalian cell differentiation. During early stages of cell differentiation, the rate of tran...
متن کامل