title: IFN-γ-mediated downregulation of LXA4 is necessary for the maintenance of nonresolving inflammation and papilloma persistence.
abstract: 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-γ receptor or neutralization of IFN-γ accelerated spontaneous papilloma regression in mice. The impaired maintenance of local inflammation was associated with reduced IFN-γ and enhanced biosynthesis of proresolution lipid mediator lipoxin A4 (LXA4). Interestingly, blocking LXA4 eliminated the effect of anti-IFN-γ, whereas treatment of mice with a therapeutic dose of LXA4 accelerated papilloma regression in an IFN-γ-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-γ and/or increasing LXA4 may be useful for the treatment of inflammation-associated tumors.
authors: Key Laboratory of Protein and Peptide Pharmaceuticals, Chinese Academy of Sciences, Beijing, China.
authors: Chunhui
authors: C
authors: Wang
authors: Mingjie
authors: M
authors: Xiao
authors: Xiaoman
authors: X
authors: Liu
authors: Chen
authors: C
authors: Ni
authors: Jianhong
authors: J
authors: Liu
authors: Ulrike
authors: U
authors: Erben
authors: Zhihai
authors: Z
authors: Qin
mesh_terms: D000818:Animals; D017209:Apoptosis; D001483:Base Sequence; D049109:Cell Proliferation; D017931:DNA Primers; D015536:Down-Regulation / Q000502:physiology*; D005434:Flow Cytometry; D007371:Interferon-gamma / Q000502:physiology*; D044045:Lipoxins / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D010212:Papilloma / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D060888:Real-Time Polymerase Chain Reaction
chemical_list: D017931:DNA Primers; D044045:Lipoxins; C040527:lipoxin A4; D007371:Interferon-gamma