Peripheral Opioid Receptor Blockade Enhances Epithelial Damage in Piroxicam-Accelerated Colitis in IL-10-Deficient Mice

Mas-Orea, Xavier; Sébert, Morgane; Benamar, Mehdi; Petitfils, Camille; Blanpied, Catherine; Saoudi, Abdelhadi; Deraison, Céline; Barreau, Frédérick; Cenac, Nicolas; Dietrich, Gilles

doi:10.3390/ijms22147387

Cited by 6 publications

(7 citation statements)

References 69 publications

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“…IL-10 is known as anti-inflammatory cytokine generated by Th2 lymphocytes and Treg cells, which plays an essential role in the orchestration of gastrointestinal homeostasis and immune tolerance [ 31 , 32 ]. Previous in vivo experiments have demonstrated that IL-10 can promote and maintain intestinal tolerance to microbiota by modulating Th1/Th17 effector responses [ 30 , 33 ]. IL-10 also plays a vital role in maintaining intestinal homeostasis [ 34 ].…”

Section: Discussionmentioning

confidence: 99%

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MiRNA-374b-5p and miRNA-106a-5p are related to inflammatory bowel disease via regulating IL-10 and STAT3 signaling pathways

Liu

et al. 2022

BMC Gastroenterol

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Background Inflammatory bowel disease (IBD), including Crohn’s disease and ulcerative colitis, is one of the most frequent gastrointestinal disorders worldwide. Although the actual etiology of IBD remains unclear, growing evidence suggests that CD4+ T cells-associated cytokines, including interferon (IFN)-γ, interleukin (IL)-10 and IL-17A, are crucial for the occurrence of IBD. It has been reported that there is a positive association between miRNAs and IBD development. In this study, we investigated the roles of hsa-miRNA-374b-5p(miRNA-374b-5p) and hsa-miRNA-106a-5p(miRNA-106a-5p) in regulating IBD development. Methods Serum was obtained from vein blood of IBD patients and healthy controls, qRT-PCR was performed to study the expression of miRNA-374b-5p and miRNA-106a-5p. Furthermore, we investigate the effects of overexpression or inhibition of miRNA-374b-5p on naïve CD4 + T cell subsets differentiation from vein blood of healthy controls by RT-qPCR, flow cytometry and western blot. And more the prediction and confirmation of the targeting genes of miRNA-374b-5p and miRNA-106a-5p were performed by bioinformatics softwares and dual-luciferase reporter assay. Results The results showed that miRNA-106a-5p and miRNA-374b-5p were significantly overexpressed in IBD patients. MiRNA-374b-5p could enhance Th1/Th17 cell differentiation and was related to IBD pathogenesis. MiRNA-374b-5p overexpression induced the mRNA expression of IL-17A and IFN-γ, and suppressed that of IL-10 in T cells. MiRNA-374b-5p inhibition decreased the mRNA expression of IL-17A and IFN-γ, while upregulated that of IL-10 in T cells. These qPCR data were further verified at protein level by western blotting and flow cytometry. In addition, dual-luciferase reporter (DLR) assay indicated that miRNA-374b-5p was directly targeted by IL-10, a key anti-inflammatory cytokine for preventing the occurrence of IBD. Meanwhile, STAT3 was identified as a target gene of miRNA-106a-5p by DLR assays. Further analysis revealed that miRNA-374b-5p regulated JAK1 and STAT3 pathways in CD4+ T cells via IL-10/STAT3 axis. MiRNA-374b-5p overexpression remarkably decreased the mRNA expression and phosphorylated (ser-727) protein levels of STAT3, while miRNA-374b-5p inhibition had the opposite effects. Conclusion MiRNA-374b-5p and miRNA-106a-5p may contribute to IBD development by regulating IL-10/STAT3 signal transduction.

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Section: Discussionmentioning

confidence: 99%

“…Defects of IL-10, IL-10-receptor-A and IL-10-receptor-B genes represent a major cause of early-onset IBD [ 35 , 36 ]. Furthermore, mice with lacking IL-10 and IL-10R are more likely to develop spontaneous colitis [ 21 , 33 , 37 , 38 ].…”

Section: Discussionmentioning

confidence: 99%

MiRNA-374b-5p and miRNA-106a-5p are related to inflammatory bowel disease via regulating IL-10 and STAT3 signaling pathways

Liu

et al. 2022

BMC Gastroenterol

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“… 133 Indeed, both IL-10- and IL-10R-deficient mice can develop spontaneous colitis. 134 , 135 Inactivation of c-MAF in Treg cells results in the dysfunction of IL-10 production, thus developing spontaneous colitis. 136 IL-10 inhibits IFN-γ production by Th1 cells in mice transferred with CD45RB hi CD4 + T cells, reduces Th17 responses in the dextran sulfate sodium (DSS) model, and enables Treg cells to suppress pathogenic Th17 cell responses in colitis.…”

Section: Immunological Pathogenesis Of Ibdmentioning

confidence: 99%

Immunology of Inflammatory Bowel Disease: Molecular Mechanisms and Therapeutics

Lu¹,

MF²,

Liang³

et al. 2022

JIR

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As a main digestive organ and an important immune organ, the intestine plays a vital role in resisting the invasion of potential pathogens into the body. Intestinal immune dysfunction remains important pathogenesis of inflammatory bowel disease (IBD). In this review, we explained the interactions among symbiotic flora, intestinal epithelial cells, and the immune system, clarified the operating mechanism of the intestinal immune system, and highlighted the immunological pathogenesis of IBD, with a focus on the development of immunotherapy for IBD. In addition, intestinal fibrosis is a significant complication in patients with long-term IBD, and we reviewed the immunological pathogenesis involved in the development of intestinal fibrogenesis and provided novel antifibrotic immunotherapies for IBD.

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“…Deletion of the IL-10 gene causes genetically engineered mice to spontaneously develop intestinal inflammation after 3 months of age [ 49 ]. In addition, nonsteroidal anti-inflammatory drugs such as piroxicam and sulindac have been recently used to accelerate and synchronize the onset of colitis [ 50 ]. Spontaneous and unremitting inflammation is driven by a Th1 T cell response that causes infiltration of lymphocytes, macrophages, and neutrophils in the colon.…”

Section: Genetically Engineered Modelsmentioning

confidence: 99%

“…49 In addition, nonsteroidal anti-inflammatory drugs such as piroxicam and sulindac have been recently used to accelerate and synchronize the onset of colitis. 50 Spontaneous and unremitting inflammation is driven by a Th1 T cell response that causes infiltration of lymphocytes, macrophages, and neutrophils in the colon. It has been revealed that the enteric microbiome plays a crucial role in immune system activation in IL-10 KO mice.…”

Section: Genetically Engineered Models Of Chronic Colitismentioning

confidence: 99%

Animal models of inflammatory bowel disease: novel experiments for revealing pathogenesis of colitis, fibrosis, and colitis-associated colon cancer

Lee,

Koh,

Radi

et al. 2023

Intest Res

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Inflammatory bowel disease (IBD), comprising Crohn’s disease and ulcerative colitis, is a lifelong disease that manifests with chronic intestinal inflammation, sequential fibrosis, and an increased risk of colitis-associated colon cancer (CAC). The combined effects of genetic, immunological, environmental, and microbial factors render it difficult to determine the specific mechanism underlying the induction and perpetuation of IBD. Various animal models of IBD have contributed enormously to the understanding of IBD pathogenesis in terms of genomics, transcriptomics, proteomics, microbiome, and drug development of novel therapeutics. Although comprehensive research on IBD has been enabled by advanced technologies, such as genetically engineered models, there is a great need to develop relevant in vivo models of colitis and fibrosis. Here, we review 4 categories of animal models of acute and chronic intestinal inflammation, fibrosis, and CAC: chemically induced, genetically engineered, T cell transfer, and spontaneous gene mutation models.

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Peripheral Opioid Receptor Blockade Enhances Epithelial Damage in Piroxicam-Accelerated Colitis in IL-10-Deficient Mice

Cited by 6 publications

References 69 publications

MiRNA-374b-5p and miRNA-106a-5p are related to inflammatory bowel disease via regulating IL-10 and STAT3 signaling pathways

MiRNA-374b-5p and miRNA-106a-5p are related to inflammatory bowel disease via regulating IL-10 and STAT3 signaling pathways

Immunology of Inflammatory Bowel Disease: Molecular Mechanisms and Therapeutics

Animal models of inflammatory bowel disease: novel experiments for revealing pathogenesis of colitis, fibrosis, and colitis-associated colon cancer

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