A rationally designed peptide IA-2-P2 against type 1 diabetes in streptozotocin-induced diabetic mice

被引：3

作者：

Shen, Lili ^{[1
]}

Lu, Shiping ^{[1
]}

Huang, Dongcheng ^{[1
]}

Li, Guoliang ^{[1
]}

Liu, Kunfeng ^{[1
]}

Cao, Rongyue ^{[1
]}

Zong, Li ^{[2
]}

Jin, Liang ^{[1
]}

Wu, Jie ^{[1
]}

机构：

[1] China Pharmaceut Univ, Sch Life Sci & Technol, Minigene Pharm Lab, Nanjing 210000, Peoples R China

[2] China Pharmaceut Univ, Inst Pharmaceut, Sch Pharm, Nanjing, Jiangsu, Peoples R China

来源：

DIABETES & VASCULAR DISEASE RESEARCH | 2017年 / 14卷 / 03期

基金：

中国国家自然科学基金;

关键词：

Type; 1; diabetes; peptide P277; insulinoma antigen-2; atherosclerosis; HEAT-SHOCK-PROTEIN; BETA-CELL FUNCTION; PHASE-II TRIAL; DOUBLE-BLIND; DIAPEP277; VACCINATION; THERAPY; ATHEROSCLEROSIS; AUTOANTIGEN; MELLITUS;

D O I：

10.1177/1479164116664189

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

Recent studies have investigated the potential of type 1 diabetes mellitus-related autoantigens, such as heat shock protein 60, to induce immunological tolerance or to suppress the immune response. A functional 24-residue peptide derived from heat shock protein 60 (P277) has shown anti-type 1 diabetes mellitus potential in experimental animals and in clinical studies, but it also carries a potential atherogenic effect. In this study, we have modified P277 to retain an anti-type 1 diabetes mellitus effect and minimize the atherogenic potential by replacing the P277 B epitope with another diabetes-associated autoantigen, insulinoma antigen-2 (IA-2), to create the fusion peptide IA-2-P2. In streptozotocin-induced diabetic C57BL/6J mice, the IA-2-P2 peptide displayed similar anti-diabetic effects to the control P277 peptide. Also, the IA-2-P2 peptide did not show atherogenic activity in a rabbit model. Our findings indicate the potential of IA-2-P2 as a promising vaccine against type 1 diabetes mellitus.

引用

页码：184 / 190

页数：7

共 25 条

[21] The role of heat shock proteins in atherosclerosis [J].

Wick, Georg ;

Jakic, Bojana ;

Buszko, Maja ;

Wick, Marius C. ;

Grundtman, Cecilia .

NATURE REVIEWS CARDIOLOGY, 2014, 11 (09) :516-529

[22] Promotion of atherosclerosis in high cholesterol diet-fed rabbits by immunization with the P277 peptide [J].

Xiong, Qiyan ;

Feng, Jiao ;

Zhang, Yu ;

Sun, Yunxiao ;

Lu, Yong ;

Li, Taiming ;

Zhang, Xiaohong ;

Cao, Rongyue ;

Jin, Liang ;

Wu, Jie .

IMMUNOLOGY LETTERS, 2016, 170 :80-87

[23] A Th2 immune shift to heat shock protein 65 fails to arrest atherosclerosis: Proatherogenic role of Th2-deviated autoantibodies [J].

Xiong, Qiyan ;

Jin, Liang ;

Li, Jianping ;

Fan, Hao ;

Cao, Rongyue ;

Wu, Jie ;

Li, Taiming ;

Liu, Jingjing .

AUTOIMMUNITY, 2009, 42 (06) :475-483

[24] Nasal immunization with heat shock protein 65 attenuates atherosclerosis and reduces serum lipids in cholesterol-fed wild-type rabbits probably through different mechanisms [J].

Xiong, Qiyan ;

Li, Jianping ;

Jin, Liang ;

Liu, Jingjing ;

Li, Taiming .

IMMUNOLOGY LETTERS, 2009, 125 (01) :40-45

[25] Antibodies to human heat-shock protein 60 are associated with the presence and severity of coronary artery disease - Evidence for an autoimmune component of atherogenesis [J].

Zhu, JH ;

Quyyumi, AA ;

Rott, D ;

Csako, G ;

Wu, HS ;

Halcox, J ;

Epstein, SE .

CIRCULATION, 2001, 103 (08) :1071-1075

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