ArticleJournal of cancer research and clinical oncology2015
The chemokine CXCL9 exacerbates chemotherapy-induced acute intestinal damage through inhibition of mucosal restitution.
Article in Journal of cancer research and clinical oncology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 20 citations in OpenAlex.
- Pediococcus pentosaceus PP34 Ameliorates 5-Fluorouracil-Induced Intestinal Mucositis via Inhibiting Oxidative Stress and Restoring the Gut Microbiota.Probiotics and antimicrobial proteins · 2025Article
- Vagus nerve modulates acute-on-chronic liver failure progression via CXCL9.Chinese medical journal · 2025Article
- LTβR-RelB signaling in intestinal epithelial cells protects from chemotherapy-induced mucosal damage.Frontiers in immunology · 2024Article
- Analysis of the interferon-γ-induced secretome of intestinal endothelial cells: putative impact on epithelial barrier dysfunction in IBD.Frontiers in cell and developmental biology · 2023Article
- Experimental Chemotherapy-Induced Mucositis: A Scoping Review Guiding the Design of Suitable Preclinical Models.International journal of molecular sciences · 2022Article
- Moxibustion attenuates inflammation in intestinal mucosal by regulating RAGE-mediated TLR4-NF-κBp65 signaling pathway in vivo and in vitro.American journal of translational research · 2022Article
- The Gut Microbiota: A Potential Gateway to Improved Health Outcomes in Breast Cancer Treatment and Survivorship.International journal of molecular sciences · 2020Review
- Changes in MMP-2, MMP-9, inflammation, blood coagulation and intestinal mucosal permeability in patients with active ulcerative colitis.Experimental and therapeutic medicine · 2020Article
- Alterations in Patterns of Gene Expression and Perturbed Pathways in the Gut-Brain Axis Are Associated With Chemotherapy-Induced Nausea.Journal of pain and symptom management · 2020Article
- The pathogenesis of mucositis: updated perspectives and emerging targets.Supportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer · 2019Review
- 5-Fluorouracil Induces Enteric Neuron Death and Glial Activation During Intestinal Mucositis via a S100B-RAGE-NFκB-Dependent Pathway.Scientific reports · 2019Article
- Effect of glutamine-enriched nutritional support on intestinal mucosal barrier function, MMP-2, MMP-9 and immune function in patients with advanced gastric cancer during perioperative chemotherapy.Oncology letters · 2017Article
- Alteration of Gut Microbiota and Inflammatory Cytokine/Chemokine Profiles in 5-Fluorouracil Induced Intestinal Mucositis.Frontiers in cellular and infection microbiology · 2017Article
- Article
- A novel genetic score model of UGT1A1 and TGFB pathway as predictor of severe irinotecan-related diarrhea in metastatic colorectal cancer patients.Journal of cancer research and clinical oncology · 2016Article
Corrections and comments
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Authors and funding
14 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
purposeAcute intestinal damage induced by chemotherapeutic agent is often a dose-limiting factor in clinical cancer therapy. The aim of this study was to investigate the effect of chemokine CXCL9 on the intestinal damage after chemotherapy and explore the therapeutic potential of anti-CXCL9 agents.
methodsIn vitro cell proliferation assay was performed with a non-tumorigenic human epithelial cell line MCF10A. Multiple pathway analysis was carried out to explore the pathway that mediated the effect of CXCL9, and the corresponding downstream effector was identified with enzyme-linked immunosorbent assays. Chemotherapy-induced mouse model of intestinal mucositis was prepared by a single injection of the chemotherapeutic agent 5-fluorouracil (5-FU). In vivo expression of cxcl9 and its receptor cxcr3 in intestinal mucosa after chemotherapy was determined by quantitative real-time PCR. Therapeutic treatment with anti-CXCL9 antibodies was investigated to confirm the hypothesis that CXCL9 can contribute to the intestinal epithelium damage induced by chemotherapy.
resultsCXCL9 inhibited the proliferation of MCF10A cells by activating phosphorylation of p70 ribosomal S6 kinase (p70S6K), which further promotes the secretion of transforming growth factor beta (TGF-β) as the downstream effector. A blockade of phospho-p70S6K with inhibitor abolished the effect of CXCL9 on MCF10A cells and reduced the secretion of TGF-β. The expression levels of cxcl9 and cxcr3 were significantly up-regulated in intestinal mucosa after 5-FU injection. Neutralizing elevated CXCL9 with anti-CXCR9 antibodies successfully enhanced reconstitution of intestinal mucosa and improved the survival rate of mice that received high-dose chemotherapy.
conclusionsCXCL9 inhibits the proliferation of epithelial cells via phosphorylation of p70S6K, resulting in the excretion of TGF-β as downstream mediator. CXCL9/CXCR3 interaction can exacerbate chemotherapeutic agent-induced intestinal damage, and anti-CXCL9 agents are potential novel therapeutic candidates for promoting mucosal restitution.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.