title: IFN-τ inhibits S. aureus-induced inflammation by suppressing the activation of NF-κB and MAPKs in RAW 264.7 cells and mice with pneumonia.
abstract: Staphylococcus aureus (S. aureus), a significant cause of pneumonia, leads to severe inflammation. Few effective treatments or drugs have been reported for S. aureus infection. Interferon tau (IFN-τ) is a type I interferon with low cellular toxicity even at high doses. Previous studies have reported that IFN-τ could significantly mitigate tissue inflammation; however, IFN-τ treatment in S. aureus-induced pneumonia has not been well reported. Thus, the aim of this study was to identify the anti-inflammatory mechanism of IFN-τ in S. aureus-induced pneumonia in mice. A S. aureus-induced pneumonia model and RAW 264.7 cells were used in this research. The histopathological as well as lung wet to dry ratio (W/D) and myeloperoxidase (MPO) activity results showed that IFN-τ could protect the lung from S. aureus damage. In addition, ELISA and qPCR revealed that IFN-τ treatment led to a decreased expression of pro-inflammatory cytokines (TNF-α, IL-1β, and IL-6) in both the cells and mouse model, but IL-10 was increased. TLR2, which is involved in the response during S. aureus infection, was also down-regulated by IFN-τ treatment and directly affected NF-κB and MAPK pathway activation. Then, we examined the phosphorylation of IκBα, NF-κB p65 and MAPKs by western blotting, and the results displayed that the phosphorylation of IκBα, NF-κB p65 and MAPKs was inhibited upon IFN-τ treatment in both the cells and mouse model. These findings indicate that IFN-τ has anti-inflammatory properties in vitro and in vivo through the inhibition of NF-κB and MAPK activation, suggesting that IFN-τ may have potential as a therapeutic agent against S. aureus-induced inflammatory diseases.
authors.affiliation: Department of Clinical Veterinary Medicine, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan 430070, People's Republic of China.
authors.forename: Gan
authors.initials: G
authors.lastname: Zhao
authors.affiliation: Department of Clinical Veterinary Medicine, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan 430070, People's Republic of China.
authors.forename: Haichong
authors.initials: H
authors.lastname: Wu
authors.affiliation: Department of Clinical Veterinary Medicine, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan 430070, People's Republic of China.
authors.forename: Kangfeng
authors.initials: K
authors.lastname: Jiang
authors.affiliation: Department of Clinical Veterinary Medicine, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan 430070, People's Republic of China.
authors.forename: Guangze
authors.initials: G
authors.lastname: Rui
authors.affiliation: Department of Clinical Veterinary Medicine, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan 430070, People's Republic of China.
authors.forename: Zhe
authors.initials: Z
authors.lastname: Zhu
authors.affiliation: Department of Clinical Veterinary Medicine, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan 430070, People's Republic of China.
authors.forename: Changwei
authors.initials: C
authors.lastname: Qiu
authors.affiliation: Department of Clinical Veterinary Medicine, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan 430070, People's Republic of China.
authors.forename: Mengyao
authors.initials: M
authors.lastname: Guo
authors.affiliation: Department of Clinical Veterinary Medicine, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan 430070, People's Republic of China. Electronic address: gzdeng1963@sohu.com.
authors.forename: Ganzhen
authors.initials: G
authors.lastname: Deng
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use*; D016207:Cytokines / Q000378:metabolism; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D006801:Humans; D007167:Immunotherapy / Q000379:methods*; D007370:Interferon Type I / Q000627:therapeutic use*; D051379:Mice; D008807:Mice, Inbred BALB C; D016328:NF-kappa B / Q000378:metabolism; D011014:Pneumonia / Q000276:immunology / Q000382:microbiology / Q000628:therapy*; D011257:Pregnancy Proteins / Q000627:therapeutic use*; D000067996:RAW 264.7 Cells; D015398:Signal Transduction / Q000187:drug effects; D013203:Staphylococcal Infections / Q000276:immunology / Q000628:therapy*; D013211:Staphylococcus aureus / Q000276:immunology*
chemical_list: D000893:Anti-Inflammatory Agents; D016207:Cytokines; D007370:Interferon Type I; D016328:NF-kappa B; D011257:Pregnancy Proteins; C020947:interferon tau; D048049:Extracellular Signal-Regulated MAP Kinases
keywords: IFN-τ; MAPKs; Nuclear factor-κB; Pneumonia