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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

IL-13 but Not IL-4 Signaling via IL-4Rα Protects Mice From Papilloma Formation During DMBA/TPA Two-Step Skin Carcinogenesis

Michael Rothe, David Quarcoo, Anna A Chashchina, Svetlana V Bozrova, Zhihai Qin, Sergei A Nedospasov, Thomas Blankenstein, Thomas Kammertoens, Marina S Drutskaya

Cancer Med. 2013 Dec;2(6):815-25.

PMID: 24403255

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-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.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
AP92240	Benz[b]anthracene		92-24-0	Price

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