Intramuscular injection of interleukin-10 plasmid DNA prevented autoimmune diabetes in mice

	Intramuscular injection of interleukin-10 plasmid DNA prevented autoimmune diabetes in mice
	Zhang, ZL; Shen, SX; Lin, B; Yu, LY; Zhu, LH; Wang, WP; Luo, FH; Guo, LH
刊名	ACTA PHARMACOLOGICA SINICA
	2003
卷号	24 期号:8 页码:751-756
关键词	interleukin-10 insulin-dependent diabetes mellitus gene therapy intramuscular injections spleen tumor necrosis factor interferon type II mice
通讯作者	Guo, LH (reprint author), Chinese Acad Sci, Shanghai Inst Biol Sci, Inst Biochem & Cell Biol, Shanghai 200031, Peoples R China.,lhguo@sunm.shcnc.ac.cn
英文摘要	To investigate the effect of plasmid coding interleukin-10 (IL-10) DNA on the development of autoimmune diabetes induced by multiple low doses of streptozotocin (STZ) in mice. METHODS: Injection of STZ (40 mg/kg, ip) was given daily for five consecutive days. pcDNA3-IL-10 plasmid (IL-10-treated group) or pcDNA3-null plasmid (pcDNA3-null-treated group) (100 mug DNA once a day) were injected into skeletal muscles of mice on d 1 and d 14. Blood glucose concentration was measured. After mice were killed on d 28, serum IFN-gamma level was measured by ELISA, and pancreatic IL-1beta and TNF-alpha mRNA expression was detected by semi-quantitative reverse-transcription PCR (RT-PCR). The number of CD4(+) and CD8(+) lymphocytes from spleen was detected using FACS. In addition, pancreatic histology was measured for determination of insulitis grades. RESULTS: Treatment with pcDNA3-IL-10 resulted in the retention and expression of the vector in skeletal muscle, associated with a considerable elevation in the plasma level of IL-10, which was not observed in pcDNA3-null-treated mice. In IL-10-treated diabetic mice induced by STZ, delay-type hypersensitivity responses were suppressed and the glucose level was greatly lower on d 14, 21, and 28 than pcDNA3-null-treated group (P<0.05 or P<0.01). On d 21 and 28 the incidence of diabetes was 33.3 % and 40.0 %, respectively, which was markedly lower than that of pcDNA3-null-treated group (P<0.05). In IL-10-treated mice pancreatic IL-1beta and TNF-alpha mRNA expression was depressed, and serum IFN-gamma concentration and the number of spleen CD4(+) or CD8(+) lymphocytes were decreased on d 28. The insulitis grades of IL-10-treated mice were lower than that of pcDNA3-null-treated group (P<0.01). CONCLUSION: Systemic administration of IL-10 plasmid DNA can alleviate insulitis of experimental autoimmune diabetes in mice and reduce incidence of diabetes.
学科主题	Chemistry; Pharmacology & Pharmacy
类目[WOS]	Chemistry, Multidisciplinary ; Pharmacology & Pharmacy
关键词[WOS]	NOD MICE ; LIPOSOME COMPLEXES ; INTERFERON-GAMMA ; GENE-TRANSFER ; STREPTOZOTOCIN ; INSULITIS ; DISEASE ; EXPRESSION ; TOXICITY ; DELIVERY
收录类别	SCI
语种	英语
WOS记录号	WOS:000184722600004
内容类型	期刊论文
版本	出版稿
源URL	[http://202.127.25.143/handle/331003/2335]
专题	上海生化细胞研究所_上海生科院生化细胞研究所
推荐引用方式 GB/T 7714	Zhang, ZL,Shen, SX,Lin, B,et al. Intramuscular injection of interleukin-10 plasmid DNA prevented autoimmune diabetes in mice[J]. ACTA PHARMACOLOGICA SINICA,2003,24(8):751-756.
APA	Zhang, ZL.,Shen, SX.,Lin, B.,Yu, LY.,Zhu, LH.,...&Guo, LH.(2003).Intramuscular injection of interleukin-10 plasmid DNA prevented autoimmune diabetes in mice.ACTA PHARMACOLOGICA SINICA,24(8),751-756.
MLA	Zhang, ZL,et al."Intramuscular injection of interleukin-10 plasmid DNA prevented autoimmune diabetes in mice".ACTA PHARMACOLOGICA SINICA 24.8(2003):751-756.