Hypoglycemic effect of<i> Lactococcus lactis</i> vaccine containing HSP65-6P277 on streptozotocin-induced type 1 diabetic mice

WU Jie; LIU Xiaorui; YANG Xue; HOU Jing; XU Maolei; SHEN Lili; HUANG Dongcheng; LIU Kunfeng

doi:10.11665/j.issn.1000-5048.20140120

Journal of China Pharmaceutical University > 2014 > 45(1): 106-110. > DOI: 10.11665/j.issn.1000-5048.20140120

WU Jie, LIU Xiaorui, YANG Xue, HOU Jing, XU Maolei, SHEN Lili, HUANG Dongcheng, LIU Kunfeng. Hypoglycemic effect of Lactococcus lactis vaccine containing HSP65-6P277 on streptozotocin-induced type 1 diabetic mice[J]. Journal of China Pharmaceutical University, 2014, 45(1): 106-110. DOI: 10.11665/j.issn.1000-5048.20140120

Citation:

PDF (1254 KB)

Hypoglycemic effect of Lactococcus lactis vaccine containing HSP65-6P277 on streptozotocin-induced type 1 diabetic mice

More Information

Graphical Abstract

Abstract

Abstract

To study the hypoglycemic effect and mechanisms of vaccine HSP65-6P277 protein on type 1 diabetic mice induced by streptozotocin(STZ), Lactococcus lactis live vector was used to express the vaccine protein. The mouse model of type 1 diabetes mellitus were established by intraperitoneal injections of multiple low dose STZ(MLD-STZ)and divided into three groups. The inducible expression strain L. lactis NZ9000 pCYT ∶HSP65-6P277, constitutive expression strain L. lactis NZ9000 pHJ ∶HSP65-6P277 and control strains L. lactis NZ9000 pCYT ∶Nuc were respectively immunized to diabetic mice orally once daily(2×10⁹ CFU, 200 μL)in the first week and once every week in the following weeks lasting for 16 weeks. Fasting blood glucose levels were measured once a month on blood samples taken from orbital venous plexus. Four months later, the mice were sacrificed. Spleen cell proliferation experiment was performed. IL-10 and IFN-γ cytokine levels of spleen cells and serum IgG levels were assayed using ELISA kits. The results showed that pCYT ∶HSP65-6P277 group and pHJ ∶HSP65-6P277 group have low blood glucose(P < 0. 05), and maintain normal body weight, compared with control group(pCYT ∶Nuc). On the other hand, cytokine IFN-γ levels were significantly lower(P < 0. 05)in spleen cells supernatant and spleen cell proliferation was reduced against HSP65 and P277(P< 0. 05), but serum IgG levels were not significantly different(P> 0. 05).
- Lactococcus lactis,
- vaccine,
- P277,
- mucosal immune,
- type 1 diabetic mellitus

FullText(HTML)

References (13)

References

[1]	Nicholas D,Odumosu O,Langridge WH.Autoantigen based vaccines for type 1 diabetes[J]. Discov Med,2011, 11(59):293-301.
[2]	Raz I,Elias D,Avron A,et al.Beta-cell function in new-onset type 1 diabetes and tyimmunomodulation with a heat-shock protein peptide(DiaPep277):a randomised,double-blind,phase II trial[J].Lancet,2001, 358(9 295):1 749-1 753.
[3]	EliasI D,Cohen R.Peptide therapy for dia NOD mice[J].Lancet,1994,343(8 899):704-706.
[4]	Cohen R,Elias D.The hsp60 peptide betes in p277 arrests the autoimmune diabetes induced by the toxin streptozotocin[J].Diabetes,1996,45(9):1 168-1 177.
[5]	Jin L,Wang Y,Xiong Q,et al.Long-lasting specific antibodies against P277 induced by mucosaladministration of P277 repeat sequences carried by Hsp65 in the absence of adjuvant[J].Vaccine,2007,25(11):2 043-2 050.
[6]	Liang J,Aihua Z,Yu W,et al.HSP65 serves as an immunogenic carrier for a diabetogenic peptide P277 inducing anti-inflammatory immune response in NOD mice by nasal administration[J]. Vaccine,2010, 28(19):3 312-3 317.
[7]	Chen QM, Wu GJ, Wu J, et al. Purification and stability research of mycobacterial heat shock protein 65 and its fusion protein Hsp65-6P277[J]. Pharm Biotechnol(药物生物技术),2007,14(4):249-254.
[8]	Huibregtse IL,Marietta EV,Rashtak S, et al.Induction of antigen-specific tolerance by oral administration of lactococcus lactis delivered immunodominant DQ8-restricted gliadin peptide in sensitized nonobese diabetic Abo Dq8 transgenic mice[J].J Immunol,2009, 183(4):2 390-2 396.
[9]	Bermúdez-Humarán LG.Lactococcus lactis as a live vector for mucosal delivery of therapeutic proteins[J]. Hum Vaccin,2009, 5(4):264-267.
[10]	Sun W,Wang L,Zhang Z,et al.Intramuscular transfer of naked calcitonin gene-related peptide gene prevents autoimmune diabetes induced bymultiple low-dose streptozotocin in C57BL mice[J]. Eur J Immunol,2003, 33(1):233-242. 　　[11] Csorba TR,Lyon AW,Hollenberg MD.Autoimmunity and the pathogenesis of type 1 diabetes[J]. Crit Rev Clin Lab Sci,2010,47(2):51-71.
[11]	Morello E,Bermúdez-Humarán LG,Llull D,et al.Lactococcus lactis an efficient cell factory for recombinant protein production and secretion[J]. J Mol Microbiol Biotech,2008, 14(1/2/3):48-58.
[12]	Takiishi T,Korf H,Van Belle TL,et al.Reversal of autoimmune diabetes by restoration of antigen-specific tolerance using genetically modified Lactococcus lactis in mice[J].J Clin Invest,2012,122(5):1 717-1 725.
[13]	Rezende RM,Oliveira RP,Medeiros SR,et al.Hsp65-producing lactococcus lactis prevents experimental autoimmune encephalomyelitis in mice by inducing CD4+LAP+regulatory T cells[J].J Autoimmun,2012,40:45-57.

[1]	CHEN Xi, JIN Liang. Research progress on sumoylation in type 2 diabetes mellitus[J]. Journal of China Pharmaceutical University, 2025, 56(1): 125-131. DOI: 10.11665/j.issn.1000-5048.2023112002
[2]	WU Yiling, YOU Qi, WU Jie. Therapeutic effect of oral vaccine based on glutamate decarboxylase 65 on streptozotocin-induced type 1 diabetic mice[J]. Journal of China Pharmaceutical University, 2021, 52(5): 614-621. DOI: 10.11665/j.issn.1000-5048.20210515
[3]	MU Jinming, LIU Yue, ZHANG Fangfang, JIN Liang. Relationship between circular RNA and type 2 diabetes and its clinical application[J]. Journal of China Pharmaceutical University, 2020, 51(3): 374-378. DOI: 10.11665/j.issn.1000-5048.20200316
[4]	LI Chengye, HUANG Wenlong, QIAN Hai. Advances in the research of long-acting strategy of insulin and GLP-1 analogs[J]. Journal of China Pharmaceutical University, 2018, 49(6): 660-670. DOI: 10.11665/j.issn.1000-5048.20180604
[5]	DU Te, CHEN Jing, SHEN Xu. Research advances in susceptibility genes of non-alcoholic fatty liver disease and its association with type 2 diabetes[J]. Journal of China Pharmaceutical University, 2018, 49(5): 537-544. DOI: 10.11665/j.issn.1000-5048.20180504
[6]	HE Dongmei, YOU Qi, WU Jie. Application of microbial vaccines in type 1 diabetes mellitus[J]. Journal of China Pharmaceutical University, 2018, 49(2): 158-164. DOI: 10.11665/j.issn.1000-5048.20180204
[7]	CAO Lanjie, ZHU Kuiniu, JIANG Cuihua, GUNN ·Jordan, CHE Chun-Tao, ZHANG Jian, YIN Zhiqi. Intervention effects of the extract of Alismatis Rhizoma on streptozotocin-induced type 2 diabetic rats[J]. Journal of China Pharmaceutical University, 2017, 48(5): 601-608. DOI: 10.11665/j.issn.1000-5048.20170516
[8]	LU Shiping, JIN Liang, WU Jie. Clinical development of type 1 diabetes vaccine[J]. Journal of China Pharmaceutical University, 2014, 45(6): 625-632. DOI: 10.11665/j.issn.1000-5048.20140603
[9]	LI Chen, YUAN Linhua, MA Xueqin, LIU Xiaoquan, XI Tao. Variation of cardiovascular risk biomarkers in type 2 diabetes mellitus[J]. Journal of China Pharmaceutical University, 2013, 44(3): 257-262. DOI: 10.11665/j.issn.1000-5048.20130314
[10]	LI Tai-ming, MA Yan-hong, XU Shu, LIU Tao, GU Chun-jiao, XU Chen, LIU Jing-jing. Preparation and preliminary analysis of activity of recombinant GLP-1 analogue[J]. Journal of China Pharmaceutical University, 2011, 42(6): 560-564.

Cited By

Get Citation

PDF

XML

Article views (1338) PDF downloads (1820)

Turn off MathJax

Article Contents

Abstract

References

Hypoglycemic effect of Lactococcus lactis vaccine containing HSP65-6P277 on streptozotocin-induced type 1 diabetic mice

Abstract

References

Related Articles

Catalog

Hypoglycemic effect of Lactococcus lactis vaccine containing HSP65-6P277 on streptozotocin-induced type 1 diabetic mice

Abstract

References

Related Articles

Catalog

Export File

Citation

Format

Content