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IL-13 but not IL-4 signaling via IL-4Rα protects mice from papilloma formation during DMBA/TPA two-step skin carcinogenesis

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Item Type:Article
Title:IL-13 but not IL-4 signaling via IL-4Rα protects mice from papilloma formation during DMBA/TPA two-step skin carcinogenesis
Creators Name:Rothe, M., Quarcoo, D., Chashchina, A.A., Bozrova, S.V., Qin, Z., Nedospasov, S.A., Blankenstein, T., Kammertoens, T. and Drutskaya, M.S.
Abstract: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-4R{alpha}(-/-) mice. We found that IL-4R{alpha}(-/-) 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 {My}g 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-4R{alpha} 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.
Keywords:Carcinogenesis, DMBA TPA, IL-13, IL-4 Receptor {alpha}, TH2, Animals, Mice
Source:Cancer Medicine
Page Range:815-825
Date:December 2013
Official Publication:https://doi.org/10.1002/cam4.145
PubMed:View item in PubMed

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