| First Author | Xiao M | Year | 2009 |
| Journal | Cancer Res | Volume | 69 |
| Issue | 5 | Pages | 2010-7 |
| PubMed ID | 19244111 | Mgi Jnum | J:145951 |
| Mgi Id | MGI:3836359 | Doi | 10.1158/0008-5472.CAN-08-3479 |
| Citation | Xiao M, et al. (2009) IFNgamma promotes papilloma development by up-regulating Th17-associated inflammation. Cancer Res 69(5):2010-7 |
| abstractText | IFNgamma plays a crucial role in immunity against a variety of transplanted tumors and methylcholanthrene-mediated tumorigenesis in mice. However, it is not clear whether and how endogenous IFNgamma influences 7,12-dimethylbenz(a)anthracene (DMBA)-induced and 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced papilloma development. We found here that IFNgamma expression was markedly up-regulated shortly after DMBA/TPA application to the skin. Surprisingly, neutralizing IFNgamma activity in vivo did not increase but rather decreased tumor development. Furthermore, IFNgamma receptor-deficient mice were also more resistant to papilloma development than their counterparts were. IFNgamma acted mainly in the promotion stage of papilloma development by enhancing TPA-induced leukocyte infiltration and epidermal hyperproliferation. The up-regulation of tumor necrosis factor alpha, interleukin (IL)-6, and transforming growth factor beta was largely dependent on host IFNgamma responsiveness. Remarkably, up-regulation of both IL-17 expression in the skin and T helper 17 (Th17) cell number in draining lymph nodes after DMBA/TPA treatment was dependent on IFNgamma signaling. Depletion of IL-17 not only decreased the DMBA/TPA-induced inflammation and keratinocyte proliferation but also delayed papilloma development. These results show that IFNgamma, under certain conditions, may promote tumor development by enhancing a Th17-associated inflammatory reaction. |
