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Interleukin-1 beta-Targeted Vaccine Improves Glucose Control and beta-Cell Function in a Diabetic KK-A(y) Mouse Model
Zha, Jun1,2; Chi, Xiao-wei3; Yu, Xiao-lin1; Liu, Xiang-meng1,4; Liu, Dong-qun1; Zhu, Jie1; Ji, Hui2; Liu, Rui-tian1
2016-05-06
Source PublicationPLOS ONE
ISSN1932-6203
Volume11Issue:5Pages:254298
AbstractInterleukin-1 beta (IL-1 beta) has been implicated as a key proinflammatory cytokine involved in the pancreatic islet inflammation of type 2 diabetes mellitus (T2DM). Excess IL-1 beta impairs islet function by inducing insulin resistance and beta-cell apoptosis. Therefore, specifically reducing IL-1 beta activity provides a therapeutic improvement for T2DM by sustaining the inhibition of IL-1 beta-mediated islet inflammation. In this study, we developed an IL-1 beta-targeted epitope peptide vaccine adjuvanted with polylactic acidmicroparticles (1 beta EPP) and applied it to a diabetic KK-A(y) mouse model. Results showed that the 1 beta EPP elicited high antibody responses, which neutralized the biological activity of IL-1 beta, and induced barely detectable inflammatory activity. 1 beta EPP immunization reduced body weight gain, protected KK-A(y) mice from hyperglycemia, improved glucose tolerance and insulin sensitivity, and decreased the serum levels of free fatty acids, total cholesterol and triglyceride. Moreover, 1 beta EPP restored beta-cell mass; inhibited beta-cell apoptosis; decreased the expression of IL-1 beta; and interrupted NF-kappa B activation by reducing IKK beta and pRelA levels. These studies indicated that the IL-1 beta-targeted vaccine may be a promising immunotherapeutic for T2DM treatment.
SubtypeArticle
WOS HeadingsScience & Technology
DOI10.1371/journal.pone.0154298
Indexed BySCI
Language英语
WOS KeywordINSULIN-RESISTANCE ; XOMA 052 ; MONOCLONAL-ANTIBODY ; IMMUNE-RESPONSES ; PLA MICROSPHERES ; INFLAMMATION ; IL-1-BETA ; MELLITUS ; MICROPARTICLES ; INTERLEUKIN-1
WOS Research AreaScience & Technology - Other Topics
WOS SubjectMultidisciplinary Sciences
Funding OrganizationNational Natural Science Foundation of China(81402837 ; National Science and Technology Major Projects of New Drugs(2014ZX09102045-005 ; 81371208) ; 2014ZX09102041-007)
WOS IDWOS:000375677000014
Citation statistics
Document Type期刊论文
Identifierhttp://ir.ipe.ac.cn/handle/122111/21056
Collection生化工程国家重点实验室
Affiliation1.Chinese Acad Sci, Inst Proc Engn, Natl Key Lab Biochem Engn, Beijing, Peoples R China
2.China Pharmaceut Univ, Sch Pharm, Nanjing 210009, Jiangsu, Peoples R China
3.Weifang Biomed Innovat & Entrepreneurship Serv Ct, Weifang, Peoples R China
4.Qilu Univ Technol, Sch Bioengn, Jinan, Peoples R China
Recommended Citation
GB/T 7714
Zha, Jun,Chi, Xiao-wei,Yu, Xiao-lin,et al. Interleukin-1 beta-Targeted Vaccine Improves Glucose Control and beta-Cell Function in a Diabetic KK-A(y) Mouse Model[J]. PLOS ONE,2016,11(5):254298.
APA Zha, Jun.,Chi, Xiao-wei.,Yu, Xiao-lin.,Liu, Xiang-meng.,Liu, Dong-qun.,...&Liu, Rui-tian.(2016).Interleukin-1 beta-Targeted Vaccine Improves Glucose Control and beta-Cell Function in a Diabetic KK-A(y) Mouse Model.PLOS ONE,11(5),254298.
MLA Zha, Jun,et al."Interleukin-1 beta-Targeted Vaccine Improves Glucose Control and beta-Cell Function in a Diabetic KK-A(y) Mouse Model".PLOS ONE 11.5(2016):254298.
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