| 19410625 |
Tao FF, Yang YF, Wang H, Sun XJ, Luo J, Zhu X, Liu F, Wang Y, Su C, Wu HW, Zhang ZS: Th1-type epitopes-based cocktail PDDV attenuates hepatic fibrosis in C57BL/6 mice with chronic Schistosoma japonicum infection. Vaccine. 2009 Jun 24;27(31):4110-7. Epub 2009 May 15.
Schistosomiasis is one of the world's major public health problems in terms of morbidity and mortality, which is characterized by a marked egg-induced CD4 (+) T-cell programmed granulomatous inflammation and cumulative fibrosis. Here PDDV (peptide-DNA dual vaccine), a widely used non-viral gene delivery system, was applied. The cocktail PDDV, based on four Th1-type epitope peptides identified from Schistosoma japonicum vaccine candidates and CpG ODN1826, could induce dominant Th1-type response in C57BL/6J mice (P <0.05). The histopathological staging and collagen assessment for fibrosis showed that the cocktail PDDV presented an obvious down-regulation effect on hepatic fibrosis caused by chronic S. japonicum infection (P <0.05), and IFN-gamma, IL-4 and IL-13 mRNAs in liver detected by RT-PCR also showed that the cocktail PDDV represented the ability to up-regulate Th1-type responses, which paralleled with a decrease expression of alpha-SMA (P <0.05) and the up-regulated MMP9/TIMP1 balance (P <0.05) when compared to the control groups. Therefore, it is indicated that the cocktail PDDV can significantly attenuate hepatic fibrosis, in parallel with the decreased HSCs activation and the up-regulated MMP9/TIMP1 balance in favor of matrix degradation, which may be partially dependent on the increased Th1 response to restore the Th1/Th2 balance. |
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