التفاصيل البيبلوغرافية
| العنوان: |
Lack of interleukin-4 receptor alpha chain-dependent signalling promotes azoxymethane-induced colorectal aberrant crypt focus formation in Balb/c mice |
| المؤلفون: |
Mark A. Hull, Brooke David Andrew, Alex F. Markham, Richard Cuthbert, PL Coletta, SL Perry, Nicolas M. Orsi, C. W. S. Ko |
| المصدر: |
The Journal of pathology. 214(5) |
| سنة النشر: |
2008 |
| مصطلحات موضوعية: |
Azoxymethane, Receptors, Cell Surface, Mouse model of colorectal and intestinal cancer, Pathology and Forensic Medicine, BALB/c, Transforming Growth Factor beta1, chemistry.chemical_compound, Mice, Interleukin-4 receptor, Medicine, Animals, Intestinal Mucosa, Receptor, Mice, Knockout, Mice, Inbred BALB C, Interleukin-13, biology, business.industry, Tumor Necrosis Factor-alpha, Interleukin, biology.organism_classification, Disease Models, Animal, Cell Transformation, Neoplastic, chemistry, Immunology, Cancer research, Carcinogens, Female, Interleukin-4, business, Colorectal Neoplasms, Precancerous Conditions, Aberrant crypt foci, Transforming growth factor, Signal Transduction |
| الوصف: |
Interleukin (IL)-4 receptor (IL-4R) α chain-dependent signalling by IL-4 and IL-13 promotes tumour growth and metastasis in mouse models of colorectal cancer. However, the role of IL-4Rα-dependent signalling during the early, pre-malignant stages of colorectal carcinogenesis has not been investigated. Therefore, we investigated the effect of deletion of the IL-4Rα gene on azoxymethane-induced colorectal aberrant crypt focus (ACF) multiplicity and size in Balb/c mice. IL-4Rα−/− mice developed significantly more ACFs [median 8, inter-quartile range (IQR) 4–11.5; n = 9] than wild-type (WT) animals (median 4, IQR 1–6; n = 9; p = 0.04, Mann–Whitney U-test). There were significantly higher levels of IL-4 in serum from azoxymethane- and sham-treated IL-4Rα−/− mice than WT animals, but no difference in serum IL-13 levels. In the absence of functional IL-4Rs, IL-13 can also signal via the IL-13Rα2 receptor, leading to induction of transforming growth factor (TGF) β, which has pro-tumourigenic activity at early stages of intestinal tumourigenesis. We found that mucosal TGFβ mRNA levels and intestinal epithelial cell TGFβ immunoreactivity were significantly higher in IL-4Rα−/− mice than inWT animals. In summary, IL-4Rα-dependent signalling has a protective, anti-neoplastic role during the post-initiation phase of azoxymethane-induced colorectal carcinogenesis in Balb/c mice. Our data should prompt thorough investigation of the role of IL-4Rα-dependent signalling during human colorectal carcinogenesis, particularly as antagonism of IL-4R signalling represents a therapeutic strategy for asthma and other allergic diseases. Copyright © 2008 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. |
| تدمد: |
0022-3417 |
| الوصول الحر: |
https://explore.openaire.eu/search/publication?articleId=doi_dedup___::ee319bc340397281d55fb614e64dda7aTest
https://pubmed.ncbi.nlm.nih.gov/18220315Test |
| حقوق: |
CLOSED |
| رقم الانضمام: |
edsair.doi.dedup.....ee319bc340397281d55fb614e64dda7a |
| قاعدة البيانات: |
OpenAIRE |
