期刊
JOURNAL OF VETERINARY MEDICAL SCIENCE
卷 76, 期 9, 页码 1241-1248出版社
JAPAN SOC VET SCI
DOI: 10.1292/jvms.14-0181
关键词
canine distemper virus; interferon-gamma; interleukin 18
资金
- Japan Society for the Promotion of Science (JSPS)
- Global COB Program Center of Education and Research for Advanced Genome-Based Medicine: for Personalized Medicine and the Control of Worldwide Infectious Diseases (Ministry of Education, Culture, Sports, Science and Technology, Japan)
- Grants-in-Aid for Scientific Research [25450421] Funding Source: KAKEN
Interleukin 18 (IL-18) plays an important role in the T-helper-cell type 1 immune response against intracellular parasites, bacteria and viral infections. It has been widely used as an adjuvant for vaccines and as an anticancer agent. However, IL-18 protein lacks a typical signal sequence and requires cleavage into its mature active form by caspase 1. In this study, we constructed mammalian expression vectors carrying cDNA encoding mature canine IL-18 (cIL-18) or mouse IL-18 (mIL-18) fused to the human IL-2 (hIL-2) signal sequence. The expressed proIL-18 proteins were processed to their mature forms in the cells. The supernatants of cells transfected with these plasmids induced high interferon-gamma production in canine peripheral blood mononuclear cells or mouse splenocytes, respectively, indicating the secretion of bioactive IL-18. Using reverse genetics, we also generated a recombinant canine distemper virus that expresses cIL-18 or mIL-18 fused to the hIL-2 signal sequence. As expected, both recombinant viruses produced mature IL-18 in the infected cells, which secreted bioactive IL-18. These results indicate that the signal sequence from hIL-2 is suitable for the secretion of mature IL-18. These recombinant viruses can also potentially be used as immunoadjuvants and agents for anticancer therapies in vivo.
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