| First Author | Rothe M | Year | 2013 |
| Journal | Cancer Med | Volume | 2 |
| Issue | 6 | Pages | 815-25 |
| PubMed ID | 24403255 | Mgi Jnum | J:320388 |
| Mgi Id | MGI:6872012 | Doi | 10.1002/cam4.145 |
| Citation | Rothe M, et al. (2013) IL-13 but not IL-4 signaling via IL-4Ralpha protects mice from papilloma formation during DMBA/TPA two-step skin carcinogenesis. Cancer Med 2(6):815-25 |
| abstractText | 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-4Ralpha(-/-) mice. We found that IL-4Ralpha(-/-) 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 mug 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-4Ralpha 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. |
