title: 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.
authors.affiliation: Department of Parasitology, Xiangya School of Medicine, Central South University, Changsha 410078, PR China.
authors.forename: Zhi
authors.initials: Z
authors.lastname: Tian
authors.forename: Xi-ya
authors.initials: XY
authors.lastname: Wang
authors.forename: Yun-fei
authors.initials: YF
authors.lastname: Zhou
authors.forename: Qi-mei
authors.initials: QM
authors.lastname: Feng
authors.forename: Shu-ju
authors.initials: SJ
authors.lastname: Zhang
authors.forename: Tie-qiu
authors.initials: TQ
authors.lastname: Yin
authors.forename: Shao-rui
authors.initials: SR
authors.lastname: Xu
authors.forename: Ying-ding
authors.initials: YD
authors.lastname: Xia
authors.forename: Jin
authors.initials: J
authors.lastname: Xu
authors.forename: Jing
authors.initials: J
authors.lastname: Jin
authors.forename: Shi-ping
authors.initials: SP
authors.lastname: Wang
mesh_terms: D000818:Animals; D018509:DNA, Helminth / Q000008:administration & dosage; D005260:Female; D020382:Interleukin-18 / Q000235:genetics* / Q000276:immunology / Q000378:metabolism; D008099:Liver / Q000276:immunology / Q000378:metabolism* / Q000469:parasitology; D008103:Liver Cirrhosis / Q000469:parasitology / Q000517:prevention & control*; D051379:Mice; D008807:Mice, Inbred BALB C; D010957:Plasmids; D011897:Random Allocation; D012549:Schistosoma japonicum / Q000235:genetics* / Q000276:immunology; D012554:Schistosomiasis japonica / Q000150:complications* / Q000276:immunology; D057127:Single-Chain Antibodies / Q000235:genetics* / Q000276:immunology / Q000378:metabolism
chemical_list: D018509:DNA, Helminth; D020382:Interleukin-18; D057127:Single-Chain Antibodies
keywords: Fusion DNA; Hepatic fibrosis; IL-18; Schistosomiasis; scFv