Experimental Study On Treatment Of Bronchial Asthma By Blockade Of GATA-3 Expression With Recombinant Interferon Gamma

Objective: To investigate the effect of recombinant IFNγ on airway inflammation, Th2 cytokine, total IgE and ovalbumin-specific IgE in serum and the expression of Transcription factor GATA-3 in murine asthmatic model, Exploring the feasibility and the mechanism of treatment bronchial asthma with recombinant IFNy/Methodes: BALB/C mice were randomly divided into four groups: group A(control group,n=12);group B(asthmatic model groups 12);group c(IFNγ intraperitoneal treated group,n=12);group D (IFNγ nebulized treated group,n=12)o The asthmatic model was established in group B, C and D by Ovalbumin(OVA) absorbed to aluminum hydroxide.PBS(0.25ml) was intraperitoneal and PBS(3ml) was nebulized in group B on day 23 to 30 once daily prior to ovalbumin challenge;IFNγ 5μg was intraperitoneal in group C started two days before the first ovalbumin challenge and given once daily prior to ovalbumin challenge;IFNγ 12μg (per aerosol per five mice)was nebulized in group D once daily prior to ovalbumin challenge;To collect the cellulal composition of bronchoalveolar lavage fluid(BALF) on day 31. The level of IL-4, IL-5 and the total IgE and ovalbumin-specific IgE in serum was determined;The airway inflammation pathology changed by Hematoxylin/eosin(HE).The expression of GATA-3 in the lung was analyzed by Immohistochemistry.Results: (1)The numbers of eosinophils in the BALF of asthmatic model group were significantly increased comparing with the control group(P<0.01); Intraperitoneal and nebulized IFNy treated group caused notably decrease of eosinophils in BALF comparing with the asthmatic model group(P<0.01).(2)The level of IL-4 and IL-5 in the BALF of asthmatic model group were significantly increasedcomparing with the control group(P<0.01); Intraperitoneal and nebulized IFNy treated group caused significant decrease of the level of IL-4 and IL-5 in BALF comparing with the astlimatic model group(/)<0.01).(3)The serum level of total IgE and ovalbumin-specific IgE in asthmatic model group were significantly increased comparing with the control group(P<0.01), Intraperitoneal and nebulized IFNy treated group caused significant decrease of the level of total IgE and ovalbumin-specific IgE in serum comparing with the asthmatic model group(P<0.01).(4)Comparing wim1 control group,bronchi smooth muscle hypertrophy, mucous hyperemia, mucous layer thickening,Inside the bronchial lumen filled with lots of mucus as well as Inflammatory cell infiltration appear in asthmatic model group. In the bronchi appear the phlegmask and around the wall of the bronchi is the Inflammatory cell infiltration While the inflammatory reaction in intraperitoneal and nebulized IFNy treated group is much less.(5) Expression of GATA-3 is rarely seen in lungs in control group while expression of GATA-3 is obviously increased in asthmatic model group.Expression of GATA-3 decreases notably in group C and D which intraperitoneal and nebulized IFNy treated was given prior to ovalbumin challenge.Conclusion: Intraperitoneal or nebulized IFNy could inhibit the level of IL-4 ^ IL-5 as well as asthnatic airway inflammation and eosinophils infiltration and the level of total IgE and ovalbumin-specific IgE in serum in mice,the mechamism may be explained by that IFNy could restrain the Th2 reaction by blockade GATA-3 expression in the lung tissue.