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IL-13 but not IL-4 signaling via IL-4Ra protects mice from papilloma formation during DMBA/TPA two-step skin carcinogenesisстатья
- Авторы: Michael Rothe, David Quarcoo, Chashchina Anna A., Bozrova Svetlana V., Zhihai Qin, Nedospasov Sergei A., Thomas Blankenstein, Thomas Kammertoens, Drutskaya Marina S.
- Журнал: Cancer Medicine
- Год издания: 2013
- DOI: 10.1002/cam4.145
- Аннотация: Interleukin 4 (IL-4) was shown to be tumor-promoting in full carcinogenesis studies using 3-methylcholanthrene (MCA). Because heretofore the role of IL-4 in DMBA/TPA (9,10-dimethyl-1,2-benz-anthracene/12-O-tetradecanoylphorbol-13-acetate) two-stage carcinogenesis was not studied, we performed such experiments using either IL-4(-/-) or IL-4Rα(-/-) mice. We found that IL-4Rα(-/-) but not IL-4(-/-) mice have enhanced papilloma formation, suggesting that IL-13 may be involved. Indeed, IL-13(-/-) mice developed more papillomas after exposure to DMBA/TPA than their heterozygous IL-13-competent littermate controls. However, when tested in a full carcinogenesis experiment, exposure of mice to 25 μg of MCA, both IL-13(-/-) and IL-13(+/-) mice led to the same incidence of tumors. While IL-4 enhances MCA carcinogenesis, it does not play a measurable role in our DMBA/TPA carcinogenesis experiments. Conversely, IL-13 does not affect MCA carcinogenesis but protects mice from DMBA/TPA carcinogenesis. One possible explanation is that IL-4 and IL-13, although they share a common IL-4Rα chain, regulate signaling in target cells differently by employing distinct JAK/STAT-mediated signaling pathways downstream of IL-13 or IL-4 receptor complexes, resulting in different inflammatory transcriptional programs. Taken together, our results indicate that the course of DMBA/TPA- and MCA-induced carcinogenesis is affected differently by IL-4 versus IL-13-mediated inflammatory cascades.
- Добавил в систему: Недоспасов Сергей Артурович
Прикрепленные файлы
| № | Имя | Описание | Имя файла | Размер | Добавлен |
|---|---|---|---|---|---|
| 1. | Полный текст | cam4.145.pdf | 1,1 МБ | 26 декабря 2014 [Pecatum] |