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 Publication | PLOS ONE
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ISSN | 1932-6203 |
Volume | 11Issue:5Pages:254298 |
Abstract | Interleukin-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. |
Subtype | Article |
WOS Headings | Science & Technology |
DOI | 10.1371/journal.pone.0154298 |
Indexed By | SCI |
Language | 英语 |
WOS Keyword | INSULIN-RESISTANCE ; XOMA 052 ; MONOCLONAL-ANTIBODY ; IMMUNE-RESPONSES ; PLA MICROSPHERES ; INFLAMMATION ; IL-1-BETA ; MELLITUS ; MICROPARTICLES ; INTERLEUKIN-1 |
WOS Research Area | Science & Technology - Other Topics |
WOS Subject | Multidisciplinary Sciences |
Funding Organization | National Natural Science Foundation of China(81402837 ; National Science and Technology Major Projects of New Drugs(2014ZX09102045-005 ; 81371208) ; 2014ZX09102041-007) |
WOS ID | WOS:000375677000014 |
Citation statistics | |
Document Type | 期刊论文 |
Identifier | http://ir.ipe.ac.cn/handle/122111/21056 |
Collection | 生化工程国家重点实验室 |
Affiliation | 1.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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Interleukin-1 beta-T(1923KB) | 期刊论文 | 出版稿 | 限制开放 | CC BY-NC-SA | Application Full Text |
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