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Interleukin-1β-Targeted Vaccine Improves Glucose Control and β-Cell Function in a Diabetic KK-Ay Mouse Model.
- Source :
- PLoS ONE, Vol 11, Iss 5, p e0154298 (2016)
- Publication Year :
- 2016
- Publisher :
- Public Library of Science (PLoS), 2016.
-
Abstract
- Interleukin-1β (IL-1β) has been implicated as a key proinflammatory cytokine involved in the pancreatic islet inflammation of type 2 diabetes mellitus (T2DM). Excess IL-1β impairs islet function by inducing insulin resistance and β-cell apoptosis. Therefore, specifically reducing IL-1β activity provides a therapeutic improvement for T2DM by sustaining the inhibition of IL-1β-mediated islet inflammation. In this study, we developed an IL-1β-targeted epitope peptide vaccine adjuvanted with polylactic acid microparticles (1βEPP) and applied it to a diabetic KK-Ay mouse model. Results showed that the 1βEPP elicited high antibody responses, which neutralized the biological activity of IL-1β, and induced barely detectable inflammatory activity. 1βEPP immunization reduced body weight gain, protected KK-Ay mice from hyperglycemia, improved glucose tolerance and insulin sensitivity, and decreased the serum levels of free fatty acids, total cholesterol and triglyceride. Moreover, 1βEPP restored β-cell mass; inhibited β-cell apoptosis; decreased the expression of IL-1β; and interrupted NF-κB activation by reducing IKKβ and pRelA levels. These studies indicated that the IL-1β-targeted vaccine may be a promising immunotherapeutic for T2DM treatment.
Details
- Language :
- English
- ISSN :
- 19326203
- Volume :
- 11
- Issue :
- 5
- Database :
- Directory of Open Access Journals
- Journal :
- PLoS ONE
- Publication Type :
- Academic Journal
- Accession number :
- edsdoj.6988aa9205a84346aa546a0c2d6afc20
- Document Type :
- article
- Full Text :
- https://doi.org/10.1371/journal.pone.0154298