Open AccessIL ‐13 but not IL ‐4 signaling via IL ‐4Rα protects mice from papilloma formation during DMBA / TPA two‐step skin carcinogenesis
Author(s) -
Rothe Michael,
Quarcoo David,
Chashchina Anna A.,
Bozrova Svetlana V.,
Qin Zhihai,
Nedospasov Sergei A.,
Blankenstein Thomas,
Kammertoens Thomas,
Drutskaya Marina S.
Publication year - 2013
Publication title -
cancer medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.403
H-Index - 53
ISSN - 2045-7634
DOI - 10.1002/cam4.145
Subject(s) - dmba , carcinogenesis , 12 o tetradecanoylphorbol 13 acetate , chemistry , cancer research , papilloma , signal transduction , biology , medicine , biochemistry , pathology , gene , phorbol ester , protein kinase c
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.