title: A protective role of IL-30 via STAT and ERK signaling pathways in macrophage-mediated inflammation.
abstract: IL-30, the p28 subunit of IL-27, interacts with the Epstein-Barr virus-induced gene 3 (EBI3) to form IL-27, which modulates the inflammatory responses in autoimmune and infectious diseases. Several previous studies have provided evidence for the role of IL-30 in the anti-inflammatory process. However, the effect of IL-30 in macrophage-mediated immune responses is not well understood. With the recent observation in our experiment, we found that IL-30 exerted potent anti-inflammatory effects in the RAW 264.7 macrophages and in a lipopolysaccharide/D-galactosamine (LPS/D-GalN)-induced mouse model. IL-30 decreased the production of tumor necrosis factor (TNF)-α and IL-6 in LPS-stimulated RAW 264.7 macrophages in a dose-dependent manner. In the macrophage-mediated GalN and LPS model of acute liver injury, IL-30 prevented liver injury by suppressing serum enzyme activity and down-regulating the pro-inflammatory cytokines TNF-α, IL-1β, IL-6, and interferon (IFN)-γ. IL-30 treatment decreased apoptosis in liver tissue and increased glutathione (GSH) levels. We postulated that IL-30 might function through gp130-mediated signaling pathways and then demonstrated that IL-30 affects LPS-induced inflammation through the STAT1, STAT3, and ERK signaling pathways. These data indicate that IL-30 can provide critical protection against macrophage-mediated liver inflammation through anti-apoptotic, anti-oxidant, and anti-inflammatory activities.
authors.affiliation: State Key Laboratory of Biotherapy, West China Hospital, West China Medical School, Sichuan University, PR China.
authors.forename: Xiao
authors.initials: X
authors.lastname: Liu
authors.forename: Zhen
authors.initials: Z
authors.lastname: Wang
authors.forename: Ning
authors.initials: N
authors.lastname: Ye
authors.forename: Zhongwen
authors.initials: Z
authors.lastname: Chen
authors.forename: Xikun
authors.initials: X
authors.lastname: Zhou
authors.forename: Xiu
authors.initials: X
authors.lastname: Teng
authors.forename: Nongyu
authors.initials: N
authors.lastname: Huang
authors.forename: Ning
authors.initials: N
authors.lastname: Liu
authors.forename: Nannan
authors.initials: N
authors.lastname: Zhang
authors.forename: Ting
authors.initials: T
authors.lastname: Guan
authors.forename: Yongqiu
authors.initials: Y
authors.lastname: Mao
authors.forename: Bin
authors.initials: B
authors.lastname: Kan
authors.forename: Yuquan
authors.initials: Y
authors.lastname: Wei
authors.forename: Jiong
authors.initials: J
authors.lastname: Li
mesh_terms: D000818:Animals; D002460:Cell Line; D006505:Hepatitis / Q000276:immunology* / Q000473:pathology*; D007155:Immunologic Factors / Q000276:immunology; D015850:Interleukin-6 / Q000276:immunology*; D007378:Interleukins / Q000276:immunology*; D020935:MAP Kinase Signaling System / Q000276:immunology*; D008262:Macrophage Activation / Q000276:immunology*; D008264:Macrophages / Q000276:immunology*; D051379:Mice; D008813:Mice, Inbred ICR; D050791:STAT Transcription Factors
chemical_list: C486767:Il27 protein, mouse; D007155:Immunologic Factors; D015850:Interleukin-6; D007378:Interleukins; D050791:STAT Transcription Factors