Th1-type epitopes-based cocktail PDDV attenuates hepatic fibrosis in C57BL/6 mice with chronic Schistosoma japonicum infection.
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.
Tao
Fang-Fang
FF
Department of Pathogen Biology, Nanjing Medical University, 140 Hanzhong Road, Nanjing, Jiangsu 210029, PR China.
Yang
Yan-Fen
YF
Wang
Hui
H
Sun
Xin-Juan
XJ
Luo
Jie
J
Zhu
Xiang
X
Liu
Feng
F
Wang
Yong
Y
Su
Chuan
C
Wu
Hai-Wei
HW
Zhang
Zhao-Song
ZS
D000199:Actins / Q000096:biosynthesis; D000276:Adjuvants, Immunologic / Q000494:pharmacology; D000818:Animals; D004247:DNA / Q000494:pharmacology; D018984:Epitopes, T-Lymphocyte / Q000235:genetics / Q000276:immunology*; D005260:Female; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis; D018793:Interleukin-13 / Q000096:biosynthesis; D015847:Interleukin-4 / Q000096:biosynthesis; D008103:Liver Cirrhosis / Q000473:pathology* / Q000517:prevention & control*; D020780:Matrix Metalloproteinase 9 / Q000096:biosynthesis; D051379:Mice; D008810:Mice, Inbred C57BL; D009838:Oligodeoxyribonucleotides; D016052:Protozoan Vaccines / Q000235:genetics / Q000276:immunology*; D012549:Schistosoma japonicum / Q000276:immunology*; D012554:Schistosomiasis japonica / Q000276:immunology* / Q000473:pathology*; D018417:Th1 Cells / Q000276:immunology; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000096:biosynthesis; D019444:Vaccines, DNA / Q000235:genetics / Q000276:immunology*
C558396:Acta2 protein, mouse; D000199:Actins; D000276:Adjuvants, Immunologic; C423449:CpG ODN 1826; D018984:Epitopes, T-Lymphocyte; D018793:Interleukin-13; D009838:Oligodeoxyribonucleotides; D016052:Protozoan Vaccines; D019715:Tissue Inhibitor of Metalloproteinase-1; D019444:Vaccines, DNA; D015847:Interleukin-4; D007371:Interferon-gamma; D004247:DNA; D020780:Matrix Metalloproteinase 9; C501830:Mmp9 protein, mouse