دورية أكاديمية
Identification of a genetic locus controlling bacteria-driven colitis and associated cancer through effects on innate inflammation.
| العنوان: | Identification of a genetic locus controlling bacteria-driven colitis and associated cancer through effects on innate inflammation. |
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| المؤلفون: | Boulard O; Translational Gastroenterology Unit, Nuffield Department of Clinical Medicine, University of Oxford, John Radcliffe Hospital, Oxford OX3 9DU, England, UK., Kirchberger S, Royston DJ, Maloy KJ, Powrie FM |
| المصدر: | The Journal of experimental medicine [J Exp Med] 2012 Jul 02; Vol. 209 (7), pp. 1309-24. Date of Electronic Publication: 2012 Jun 25. |
| نوع المنشور: | Journal Article; Research Support, Non-U.S. Gov't |
| اللغة: | English |
| بيانات الدورية: | Publisher: Rockefeller University Press Country of Publication: United States NLM ID: 2985109R Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1540-9538 (Electronic) Linking ISSN: 00221007 NLM ISO Abbreviation: J Exp Med Subsets: MEDLINE |
| أسماء مطبوعة: | Original Publication: New York, NY : Rockefeller University Press |
| مواضيع طبية MeSH: | Colitis/*genetics , Colorectal Neoplasms/*genetics , Genetic Loci/*genetics , Genetic Predisposition to Disease/*genetics , Helicobacter Infections/*genetics, Animals ; Azoxymethane/toxicity ; Carcinogens/toxicity ; Chromosome Mapping ; Chromosomes, Mammalian/genetics ; Colitis/immunology ; Colitis/microbiology ; Colorectal Neoplasms/immunology ; Colorectal Neoplasms/microbiology ; Disease Resistance/drug effects ; Disease Resistance/genetics ; Disease Resistance/immunology ; Helicobacter Infections/immunology ; Helicobacter Infections/microbiology ; Helicobacter hepaticus/immunology ; Helicobacter hepaticus/physiology ; Host-Pathogen Interactions/immunology ; Humans ; Immunity, Innate/genetics ; Immunity, Innate/immunology ; Inflammation/genetics ; Inflammation/immunology ; Mice ; Mice, 129 Strain ; Mice, Inbred C3H ; Mice, Inbred C57BL ; Mice, Knockout ; Polymorphism, Single Nucleotide ; Telomere/genetics |
| مستخلص: | Chronic inflammation of the intestine has been associated with an elevated risk of developing colorectal cancer. Recent association studies have highlighted the role of genetic predisposition in the etiology of colitis and started to unravel its complexity. However, the genetic factors influencing the progression from colon inflammation to tumorigenesis are not known. We report the identification of a genetic interval Hiccs that regulates Helicobacter hepaticus-induced colitis and associated cancer susceptibility in a 129.RAG(-/-) mouse model. The 1.7-Mb congenic interval on chromosome 3, containing eight genes and five microRNAs, renders susceptible mice resistant to colitis and reduces tumor incidence and multiplicity. Bone marrow chimera experiments showed that resistance is conferred by the hematopoietic compartment. Moreover, the Hiccs locus controls the induction of the innate inflammatory response by regulating cytokine expression and granulocyte recruitment by Thy1(+) innate lymphoid cells. Using a tumor-promoting model combining chronic Helicobacter hepaticus infection and the carcinogen azoxymethane, we found that Hiccs also regulates the frequency of colitis-associated neoplasia. Our study highlights the importance of innate immune cells and their genetic configuration in driving progression from inflammation toward cancer and opens the door for analysis of these pathways in human inflammatory disorders and associated cancers. |
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| معلومات مُعتمدة: | 095688 United Kingdom WT_ Wellcome Trust; A7297 United Kingdom CRUK_ Cancer Research UK; A11663 United Kingdom CRUK_ Cancer Research UK; United Kingdom WT_ Wellcome Trust; 086354 United Kingdom WT_ Wellcome Trust |
| المشرفين على المادة: | 0 (Carcinogens) MO0N1J0SEN (Azoxymethane) |
| تواريخ الأحداث: | Date Created: 20120627 Date Completed: 20120928 Latest Revision: 20230610 |
| رمز التحديث: | 20231215 |
| مُعرف محوري في PubMed: | PMC3405508 |
| DOI: | 10.1084/jem.20120239 |
| PMID: | 22734048 |
| قاعدة البيانات: | MEDLINE |
| تدمد: | 1540-9538 |
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| DOI: | 10.1084/jem.20120239 |