ABSTRACT
In order to investigate the anti-tumor angiogenesis activity with a recombinant Ag43/FGFR1 chimeric protein(AF)vaccine in a mouse H22 hepatoma model,tumor volume and survival rate of the mice were studied at a 3-day interval,Microvessel density(MVD)was detected by immunohistochemistry.The endothelial deposition of autoantibodies within tumor tissues was examined by immunofluorescent staining,and anti-FGFR1 antibody-producing B cells(APBCs)were tested by enzyme-linked immunospot(ELISPOT)assay.Compared with the three control groups,the tumor volume was significantly decreased and the survival time was significantly prolonged in AF-immunized group(P<0.05).The number of APBCs in AF-immunized mice(129.6±10.9)was more than in controls[6.2±1.1(FGFR1),6.0±1.2(Ag43)and 5.2±1.4(NS),P<0.01].Moreover,the endothelial deposition of autoantibodies was found in tumor tissues from AF-immunized mice,but not in control groups.MVD in AF-immunized group was significantly lower than in FGFR1-immunized group,Ag43-immunized group and NS group(10.3±3.1 vs 39.4±8.6 vs 42.3±9.8 and 43.6±10.6,P<0.01).These findings demonstrated that the AF protein vaccine effectively inhibited tumor angiogenesis and growth via production of autoantibodies against self-FGFR1.
ABSTRACT
Interleukin-5 (IL-5) involves in the development of airway inflammation and hyperresponsiveness through activation of eosinophils. Thus, inhibition of IL-5 expression seems to be an attractive approach for asthma therapy. In this study, an antisense IL-5 gene transferred by recombinant adeno-associated virus (asIL-5) was constructed to transfect murine allergic asthma model. Our results showed that asIL-5 efficiently inhibited the IL-5 mRNA expression and significantly attenuated the inflammation in lung tissues. Significant decreasing of eosino-phils and inflammatory cells were found in peripheral blood and bronchoalveolar lavage fluid (BALF). In addition, significant inhibition of airway hyperresponsiveness (AHR) was also found in the mice treated with asIL-5. These observations demonstrate that antisense oligonucleotid against IL-5 delivered by adeno-associated virus system is possibly an efficacious therapeutic strategy for allergic asthma and other eosinophil-related disorders.