Low Doses of Exogenous Interferon-gamma Attenuated Airway Inflammation Through Enhancing Fas/FasL-Induced CD4(+) T Cell Apoptosis in a Mouse Asthma Model

作者：Yao Yinan; Lu Shan; Li Hequan; Lu Guohua; Zhou Jianying^*

来源：Journal of Interferon and Cytokine Research, 2012, 32(11): 534-541.

DOI：10.1089/jir.2012.0016

To investigate whether low doses of exogenous interferon (IFN)-gamma 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-gamma 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-gamma doses on Fas/FasL expression and CD4(+) T cell apoptosis were assessed in vitro. We demonstrated that low doses of IFN-gamma reduced pulmonary infiltration of inflammatory cells, Th2 cytokine production, and goblet cells hyperplasia (P < 0.05), while high doses of endogenous IFN-gamma had almost no effect. We also found that low doses of IFN-gamma 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-gamma 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-gamma, which attenuate airway inflammation through enhancing Fas/FasL-induced CD4(+) T cell apoptosis.

• 出版日期2012-11
• 单位浙江大学