| First Author | Wang C | Year | 2013 |
| Journal | Cancer Res | Volume | 73 |
| Issue | 6 | Pages | 1742-51 |
| PubMed ID | 23319805 | Mgi Jnum | J:196903 |
| Mgi Id | MGI:5490180 | Doi | 10.1158/0008-5472.CAN-12-2801 |
| Citation | Wang C, et al. (2013) IFN-gamma-mediated downregulation of LXA4 is necessary for the maintenance of nonresolving inflammation and papilloma persistence. Cancer Res 73(6):1742-51 |
| abstractText | Nonresolving inflammation is a hallmark of many types of tumors and the molecular mechanisms maintaining this inflammation are still largely unknown. In a two-stage carcinogenesis model, we observed here that the lack of IFN-gamma receptor or neutralization of IFN-gamma accelerated spontaneous papilloma regression in mice. The impaired maintenance of local inflammation was associated with reduced IFN-gamma and enhanced biosynthesis of proresolution lipid mediator lipoxin A4 (LXA4). Interestingly, blocking LXA4 eliminated the effect of anti-IFN-gamma, whereas treatment of mice with a therapeutic dose of LXA4 accelerated papilloma regression in an IFN-gamma-independent manner. These results link for the first time a cytokine-dependent maintenance of inflammation with a downregulated production of proresolution lipid mediators. Strategies promoting spontaneous resolution of chronic inflammation by blocking IFN-gamma and/or increasing LXA4 may be useful for the treatment of inflammation-associated tumors. |
