ArticleMucosal immunology2017
Interleukin-22 drives nitric oxide-dependent DNA damage and dysplasia in a murine model of colitis-associated cancer.
Article in Mucosal immunology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers.
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Who cites it
43 citing papers in PubMed, 64 citations in OpenAlex.
- Nitric Oxide in the Intestinal Stem Cell Niche: A Spatial Model of Nitrosative Stress and Clonal Evolution in Colitis-Associated Colorectal Cancer.Digestive diseases and sciences · 2026Review
- Cellular senescence in Crohn's disease: a double-edged sword in intestinal fibrosis.Frontiers in immunology · 2026Review
- Expression of Interleukin 23 and Interleukin 28 in Mucinous & Non-Mucinous Colorectal Carcinoma and Their Relation to Clinicopathological Features and Prognosis.Asian Pacific journal of cancer prevention : APJCP · 2025Article
- Ulcerative colitis and colorectal cancer: Pathogenic insights and precision strategies for prevention and treatment.World journal of gastrointestinal oncology · 2025Review
- Evaluating IL22RA1 expression as a predictive indicator in human colon cancer progression.BMC cancer · 2025Article
- Emerging role of small RNAs in inflammatory bowel disease and associated colorectal cancer (Review).International journal of molecular medicine · 2025Review
- Type 17 immunity: novel insights into intestinal homeostasis and autoimmune pathogenesis driven by gut-primed T cells.Cellular & molecular immunology · 2024Review
- Colonic expression of glutathioneHeliyon · 2023Article
- Interleukins (Cytokines) as Biomarkers in Colorectal Cancer: Progression, Detection, and Monitoring.Journal of clinical medicine · 2023Review
- How autophagy, a potential therapeutic target, regulates intestinal inflammation.Frontiers in immunology · 2023Review
- High iNOS and IL-1β immunoreactivity are features of colitis-associated colorectal cancer tumors, but fail to predict 5-year survival.Upsala journal of medical sciences · 2023Article
- Article
- Decreased NHE3 expression in colon cancer is associated with DNA damage, increased inflammation and tumor growth.Scientific reports · 2022Article
- The Role of Inflammatory Cytokines in the Pathogenesis of Colorectal Carcinoma-Recent Findings and Review.Biomedicines · 2022Review
- Inflammatory bowel disease and carcinogenesis.Cancer metastasis reviews · 2022Review
- Article
- IFN-γ activates the tumor cell-intrinsic STING pathway through the induction of DNA damage and cytosolic dsDNA formation.Oncoimmunology · 2022Article
- Inflammatory Bowel Disease-Associated Colorectal Cancer: Translational Risks from Mechanisms to Medicines.Journal of Crohn's & colitis · 2021Review
- Acetaminophen-Induced Liver Injury Exposes Murine IL-22 as Sex-Related Gene Product.International journal of molecular sciences · 2021Article
- Signaling pathways in intestinal homeostasis and colorectal cancer: KRAS at centre stage.Cell communication and signaling : CCS · 2021Review
Corrections and comments
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Authors and funding
16 authors at 3 institutions in 1 country.
Funding
Abstract
The risk of colon cancer is increased in patients with Crohn's disease and ulcerative colitis. Inflammation-induced DNA damage could be an important link between inflammation and cancer, although the pathways that link inflammation and DNA damage are incompletely defined. RAG2-deficient mice infected with Helicobacter hepaticus (Hh) develop colitis that progresses to lower bowel cancer. This process depends on nitric oxide (NO), a molecule with known mutagenic potential. We have previously hypothesized that production of NO by macrophages could be essential for Hh-driven carcinogenesis, however, whether Hh infection induces DNA damage in this model and whether this depends on NO has not been determined. Here we demonstrate that Hh infection of RAG2-deficient mice rapidly induces expression of iNOS and the development of DNA double-stranded breaks (DSBs) specifically in proliferating crypt epithelial cells. Generation of DSBs depended on iNOS activity, and further, induction of iNOS, the generation of DSBs, and the subsequent development of dysplasia were inhibited by depletion of the Hh-induced cytokine IL-22. These results demonstrate a strong association between Hh-induced DNA damage and the development of dysplasia, and further suggest that IL-22-dependent induction of iNOS within crypt epithelial cells rather than macrophages is a driving force in this process.
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Registered trials
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.