Peters, Sebastian and Grunwald, Nicole and Ruemmele, Petra and Endlicher, Esther and Lechner, Anja and Neumann, Inga D. and Obermeier, Florian and Reber, Stefan O. (2012) Chronic psychosocial stress increases the risk for inflammation-related colon carcinogenesis in male mice. STRESS-THE INTERNATIONAL JOURNAL ON THE BIOLOGY OF STRESS, 15 (4). pp. 403-415. ISSN 1025-3890, 1607-8888
Full text not available from this repository. (Request a copy)Abstract
Patients with inflammatory bowel diseases (IBDs) have a higher risk of developing colorectal cancer (CRC) than the general population. Furthermore, chronic psychosocial stress increases the likelihood of developing IBD and multiple types of malignant neoplasms, including CRC. Here, for the first time, we investigate the effects of chronic psychosocial stress in male mice on an artificially induced CRC, by employing the chronic subordinate colony (CSC) housing paradigm in combination with the reliable azoxymethane (AOM)/dextran sodium sulfate (DSS) CRC model. Colonoscopy revealed that CSC mice showed accelerated macroscopic suspect lesions. In addition, more CSC mice developed low-grade dysplasia (LGD) and/or high-grade dysplasia (HGD) in the colonic tissue compared to the single-housed control mice (SHC). CSC mice showed an increased number of Ki67(+) and a decreased number of terminal deoxynucleotidyl transferase dUTP nick end labeling epithelial cells in colonic tissue. Colonic liver receptor homolog-1 (LRH-1), cyclooxygenase II (COXII), tumor necrosis factor, forkhead box P3 (FoxP3) mRNA as well as colonic beta-catenin, COXII, and LRH-1 protein expression were also increased in CSC compared with SHC mice. Although the number of CD4(+) Th cells was increased, a tendency toward a decreased colonic interferon-gamma (IFN-gamma) mRNA expression was observed. Furthermore, despite an increased percentage of CD3(+) cells and CD3(+)/FoxP3(+) double-positive cells within mesenteric lymph node cells of CSC mice, IFN-gamma secretion from these cells was unaffected. Altogether, our results suggest that chronic psychosocial stress increases the risk for AOM/DSS-induced and, thus, inflammation-related CRC. Finally, assessment of additional time points may test whether the shift from tumor-protective Th1 cell to regulatory T-cell immunity represents a consequence of increased carcinogenesis or a causal factor involved in its development.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | DEXTRAN SODIUM-SULFATE; DSS-INDUCED COLITIS; ULCERATIVE-COLITIS; COLORECTAL-CANCER; CELL-PROLIFERATION; TUMOR-METASTASIS; CROHNS-DISEASE; BOWEL-DISEASE; BETA-CATENIN; AZOXYMETHANE; Azoxymethane; chronic psychosocial stress; colitis; colorectal cancer; inflammation; regulatory T cells |
| Subjects: | 500 Science > 570 Life sciences 500 Science > 590 Zoological sciences 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Immunologie Medicine > Lehrstuhl für Innere Medizin I Medicine > Lehrstuhl für Pathologie Biology, Preclinical Medicine > Institut für Zoologie Biology, Preclinical Medicine > Institut für Zoologie > Tierphysiologie/Neurobiologie (Prof. Dr. Inga Neumann) |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 12 May 2020 05:22 |
| Last Modified: | 12 May 2020 05:22 |
| URI: | https://pred.uni-regensburg.de/id/eprint/18551 |
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