RNA-Seq approach to investigate the effects of melatonin on bone marrow-derived dendritic cells from dextran sodium sulfate-induced colitis mice. (November 2022)

• Record Type: Journal Article
• Authors: Feng, Sisi; Xu, Zhenguo; Zhang, Zhiguang; Mo, Yiqun; Deng, Yujie; Li, Li; Fei, Shuting; Wu, Jiamin; Wang, Kaifang; Zhang, Qunwei; Song, Jun; Zhou, Ruixiang
• Is Part Of: Toxicology. Volume 481(2022)
• Publication Date: 2022-11
• Subjects: BM bone marrow -- BMDC bone marrow-derived DC -- BP biological process -- CC cellular component -- circRNA circular RNA -- DAI disease activity index -- DC dendritic cell -- DEGs differentially expressed genes -- DSS dextran sulfate sodium -- GM-CSF murine granulocyte-macrophage colony stimulating factor -- IBD inflammatory bowel disease -- IFN-γ Interferon-γ -- IL interleukin -- LPS lipopolysaccharide -- lncRNA long ncRNA -- MF molecular function -- MLT melatonin -- ncRNAs non-coding Ribose Nucleic Acids -- PCC Pearson's correlation coefficient -- UC ulcerative colitis; Melatonin -- Non-coding RNAs -- Bone marrow dendritic cells -- Inflammatory bowel disease -- RNA sequencing; Toxicology -- Periodicals; Chemicals -- Physiological effect -- Periodicals; 615.9005
• DOI: 10.1016/j.tox.2022.153354
• Languages: English
• ISSNs: 0300-483X

Abstract

Abstract: Melatonin (MLT) was reported to have therapeutic effects on inflammatory bowel disease (IBD) such as ulcerative colitis (UC) and Crohn's disease (CD) due to its anti-inflammatory and immunomodulatory properties. However, whether the beneficial effects of melatonin on colitis are through altering the immune response of bone marrow-derived dendritic cells (BMDCs) has not been well characterized. Here, we propose that MLT alleviates dextran sulfate sodium (DSS)-induced colitis in mice through its regulation of the immune response of BMDCs, in which some lncRNA, circRNA, miRNA, and mRNA may be involved. We at first established a DSS-induced colitis mouse model and found that the concentration of MLT in the serum of DSS-induced colitis mice was significantly lower than that in the control mice. Supplementation with MLT alleviated DSS-induced colitis in mice, which was reflected by preventing mouse body weight loss, colon length shortening, inflammation, and epithelial tissue destruction and abscission in the colon. We then isolated and cultured BMDCs and found that MLT could inhibit the activation of BMDCs from the colitis mice, which was reflected by reducing the phagocytotic ability of the cells, inhibiting their migration, and decreasing their secretion of pro-inflammatory cytokines. RNA sequencing results showed that MLT promoted the transformation of BMDCs into immune tolerant phenotypes in DSS-induced colitis mice through affecting non-coding RNAs (ncRNAs). Among them, lncRNA ENSMUST00000226323, circRNA-0520, and circRNA-2243 were predicted to interact with miRNA-709, and mRNAs of Ywhaz and Ccl9 were the targets of miRNA-709, all of which were involved in MLT-induced alteration of BMDCs functions in DSS-induced colitis mice via PI3K-Akt pathway. Our findings may provide some clues for understanding MLT inhibiting inflammatory response in DSS-induced colitis, which may be through alteration of BMDCs function. Graphical Abstract: ga1 Highlights: MLT alleviated DSS-induced colitis in mice through its regulation of the immune response in BMDCs. MLT inhibited phagocytosis, migration, and proinflammatory cytokine production of BMDCs from the colitis mice. MLT promoted the transformation of BMDCs into immune tolerant phenotypes in colitis through affecting ncRNAs. lncRNA_ENSMUST00000226323, circRNA-0520, and circRNA-2243 were predicted to interact with miR-709. Ywhaz and CCL19 were the targets of miR-709 and involved in altered PI3K-Akt pathway in colitis.