Serum Amyloid A Promotes Inflammation-Associated Damage and Tumorigenesis in a Mouse Model of Colitis-Associated Cancer
| Autor: | Preetha Shridas, Anna-Mart Engelbrecht, Frederick C. de Beer, Willem J.S. de Villiers, Daleen Conradie, Tanja Davis |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
Colorectal cancer
Macrophage medicine.medical_treatment RC799-869 Inflammatory bowel disease Mice AOM azoxymethane SAA serum amyloid A Protein Isoforms apoSAA acute-phase serum amyloid A Intestinal Mucosa qPCR quantitative real-time polymerase chain reaction Original Research Mice Knockout TNF tumor necrosis factor Colon Cancer IBD inflammatory bowel disease Gastroenterology Diseases of the digestive system. Gastroenterology Serum Amyloid A Immunohistochemistry Interleukin 10 Cytokine Cell Transformation Neoplastic Tumor necrosis factor alpha Disease Susceptibility DAI disease activity index medicine.symptom CAC colitis-associated cancer Inflammation MCM2 Minichromosome maintenance 2 protein DSS dextran sulfate sodium medicine Animals Serum amyloid A SAADKO serum amyloid A double-knockout Serum Amyloid A Protein Hepatology business.industry Macrophages Cancer medicine.disease IL interleukin Disease Models Animal Cancer research Colitis-Associated Cancer Colitis-Associated Neoplasms business Biomarkers |
| Zdroj: | Cellular and Molecular Gastroenterology and Hepatology Cellular and Molecular Gastroenterology and Hepatology, Vol 12, Iss 4, Pp 1329-1341 (2021) |
| ISSN: | 2352-345X |
| Popis: | Background & Aims Identifying new approaches to lessen inflammation, as well as the associated malignant consequences, remains crucial to improving the lives and prognosis of patients diagnosed with inflammatory bowel diseases. Although it previously has been suggested as a suitable biomarker for monitoring disease activity in patients diagnosed with Crohn’s disease, the role of the acute-phase protein serum amyloid A (SAA) in inflammatory bowel disease remains unclear. In this study, we aimed to assess the role of SAA in colitis-associated cancer. Methods We established a model of colitis-associated cancer in wild-type and SAA double-knockout (Saa1/2-/-) mice by following the azoxymethane/dextran sulfate sodium protocol. Disease activity was monitored throughout the study while colon and tumor tissues were harvested for subsequent use in cytokine analyses, Western blot, and immunohistochemistry +experiments. Results We observed attenuated disease activity in mice deficient for Saa1/2 as evidenced by decreased weight loss, increased stool consistency, decreased rectal bleeding, and decreased colitis-associated tissue damage. Macrophage infiltration, including CD206+ M2-like macrophages, also was attenuated in SAA knockout mice, while levels of interleukin 4, interleukin 10, and tumor necrosis factor-ɑ were decreased in the distal colon. Mice deficient for SAA also showed a decreased tumor burden, and tumors were found to have increased apoptotic activity coupled with decreased expression for markers of proliferation. Conclusion Based on these findings, we conclude that SAA has an active role in inflammatory bowel disease and that it could serve as a therapeutic target aimed at decreasing chronic inflammation and the associated risk of developing colitis-associated cancer. Graphical abstract |
| Databáze: | OpenAIRE |
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