Schistosoma japonicum scFv-IL18 fusion DNA ameliorates hepatic fibrosis in schistosomiasis-infected mice via improving local concentration of IL-18 in liver.

Abstract:

:The pathogenesis of chronic schistosomiasis is caused by irritation of the schistosome eggs trapped in liver that induce delayed hypersensitive reactions from the surrounding tissues, leading to the formation of inflammatory granuloma and subsequent fibrosis. A Schistosoma japonicum (S. japonicum) single-chain fragment variable (SjscFv) which specifically binds to the S. japonicum soluble immature egg antigen (SIEA) can be used as a target to deliver specific cytokine towards the site of hepatic fibrosis. To test this hypothesis, a novel recombinant plasmid, pVAX1/SjscFv-IL18, was constructed by fusing SjscFv to IL-18 gene with a 45bp glycine-rich linker. Furthermore, experiments on mice showed that pVAX1/SjscFv-IL18 could effectively express IL-18 in the liver and in serum. Hepatic contents of IL-2 and IFN-γ (Th1-type) in S. japonicum-infected mice vaccinated with pVAX1/SjscFv-IL18 increased significantly but those of their IL-4 and IL-10 (Th2-type) decreased as compared to the analyzed results of 4 cytokines in the liver cells of control mice vccinated with pVAX1/IL18. Consistent with the levels of Th1 and Th2 cytokines, mice vaccinated with pVAX1/SjscFv-IL18 developed much less hepatic fibrosis 20weeks after infection, which was evaluated by average volumn of granuloma and collagen contents. These data suggested that the linkage of IL-18 to the target-specific SjscFv molecule appears to be a potentially promising trial route of therapy, the hepatic fibrosis in S. japonicum-infected mice may be ameliorated through effective expression of IL18 in liver.

journal_name

Exp Parasitol

authors

Tian Z,Wang XY,Zhou YF,Feng QM,Zhang SJ,Yin TQ,Xu SR,Xia YD,Xu J,Jin J,Wang SP

doi

10.1016/j.exppara.2013.05.002

subject

Has Abstract

pub_date

2013-08-01 00:00:00

pages

447-54

issue

4

eissn

0014-4894

issn

1090-2449

pii

S0014-4894(13)00131-8

journal_volume

134

pub_type

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