title: Low doses of exogenous interferon-γ attenuated airway inflammation through enhancing Fas/FasL-induced CD4+ T cell apoptosis in a mouse asthma model.
abstract: To investigate whether low doses of exogenous interferon (IFN)-γ attenuate airway inflammation, and the underlying mechanisms, in asthma. C57BL/6 mice (n=42), after intraperitoneal ovalbumin (OVA) sensitization on day 0 and day 12, were challenged with OVA aerosol for 6 consecutive days. Different doses of IFN-γ were then administered intraperitoneally 5 min before each inhalation during OVA challenge. Airway hyperresponsiveness, airway inflammatory cells, cytokine profiles, and Fas/FasL expression on CD4(+) T cells were evaluated in an asthma model. The effect of various IFN-γ doses on Fas/FasL expression and CD4(+) T cell apoptosis were assessed in vitro. We demonstrated that low doses of IFN-γ reduced pulmonary infiltration of inflammatory cells, Th2 cytokine production, and goblet cells hyperplasia (P<0.05), while high doses of endogenous IFN-γ had almost no effect. We also found that low doses of IFN-γ relocated Fas/FasL to the CD4(+) T cell surface in the asthma model (P<0.05) and increased FasL-induced apoptosis in vitro (P<0.05). Furthermore, treatment with MFL-3, an anti-FasL antibody, partially abolished the anti- inflammatory properties of IFN-γ in the airway rather than affecting the Th1/Th2 balance. This research has revealed an alternative mechanism in asthma that involves low doses of IFN-γ, which attenuate airway inflammation through enhancing Fas/FasL-induced CD4(+) T cell apoptosis.
authors.affiliation: Department of Respiratory Diseases, The First Affiliated Hospital of College of Medicine, Zhejiang University, Republic of China.
authors.forename: Yinan
authors.initials: Y
authors.lastname: Yao
authors.forename: Shan
authors.initials: S
authors.lastname: Lu
authors.forename: Hequan
authors.initials: H
authors.lastname: Li
authors.forename: Guohua
authors.initials: G
authors.lastname: Lu
authors.forename: Jianying
authors.initials: J
authors.lastname: Zhou
mesh_terms: D000818:Animals; D017209:Apoptosis; D001249:Asthma / Q000188:drug therapy / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism / Q000502:physiology; D016207:Cytokines / Q000096:biosynthesis; D053222:Fas Ligand Protein / Q000276:immunology / Q000378:metabolism*; D007371:Interferon-gamma / Q000008:administration & dosage* / Q000276:immunology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D010047:Ovalbumin; D012137:Respiratory System / Q000276:immunology; D058408:Th1-Th2 Balance / Q000187:drug effects; D019014:fas Receptor / Q000378:metabolism
chemical_list: D016207:Cytokines; D053222:Fas Ligand Protein; C491899:Fas protein, mouse; C505658:Fasl protein, mouse; D019014:fas Receptor; D007371:Interferon-gamma; D010047:Ovalbumin