Selective inhibition of IL-2 gene expression by IL-2 antisense oligonucleotides blocks heart allograft rejection.
Selective inhibition of IL-2 gene expression by IL-2 antisense oligonucleotides blocks heart allograft rejection.
复制标题
IL-2 反义寡核苷酸选择性抑制 IL-2 基因表达可阻止心脏同种异体移植排斥。
DOI：
10.1097/00007890-200109150-00029
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发表时间：
2001
期刊：
影响因子：
6.2
通讯作者：
Stepkowski,SM
中科院分区：
文献类型：
--
作者：
Qu,X;Kirken,RA;Tian,L;Wang,M;Bennett,CF;Stepkowski,SM
Purpose.We tested the effects of selective inhibition of interleukin (IL)-2 gene expression by IL-2 antisense oligonucleotide (oligo) with phosphorothioate (PS)/phosphodiester (PD)/2′-methoxyethyl (ME) modifications (17359) on T-cell function and the survival of heart allografts in mice.Methods.The PS-(17328) or PS/PD/ME-(17359) IL-2 oligo was electroporated to mouse T cell lymphoma cells (TIB 155) stimulated with concanavalin A (Con A). Expression of IL-2 was analyzed by an ELISA spot assay and a reverse transcript polymerase chain reaction method. C3H (H-2 k) mice transplanted with BALB/c (H-2 d) heart grafts were treated iv with a 7-day osmotic pump with 20 mg/kg 17359 alone or in combination with sirolimus (SRL).Results.In comparison with untreated controls, 500 to 2000 nM 17328 inhibited IL-2 protein production by 21.8% to 47.2%, whereas 500 to 2000 nM 17359 did so by 35.5% to 83.5%(both P< 0.001). In vivo, 20 mg/kg 17359 prolonged survivals to a mean survival time (MST) of 18.3±2.6 days (P< 0.001) in comparison with only 8.2±0.8 days in untreated controls. Although 0.2 mg/kg SRL alone produced a MST of 18.8±6.0 days (P< 0.01), addition of 20 mg/kg 17539 synergistically extended survivals to 54.3±12.1 days (P< 0.001). As expected, IL-2 mRNA, but not IL-7, IL-9, or IL-15 mRNA, was reduced in allografts from recipients treated with 17359 compared with untreated controls. Lymph node cells from the same recipients displayed reduction in proliferative response to donor alloantigen and in generation of alloantigen-specific cytotoxic T cells.Conclusion.Selective inhibition of IL-2 mRNA in vivo inhibits T-cell function and extends allograft survival.
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影响因子：
6.2
作者：
Andoh, TF;Lindsley, J;Bennett, WM
通讯作者：
Bennett, WM
第二代反义寡核苷酸：从核酸酶抗性到动物生物功效
影响因子：
1.2
作者：
K. Altmann;N. Dean;D. Fabbro;S. Freier;T. Geiger;R. Häner;D. Hüsken;Pierre Martin;B. Monia;M. Müller;F. Natt;P. Nicklin;J. Phillips;U. Pieles;H. Sasmor;H. Moser
通讯作者：
H. Moser
口服西罗莫司和环孢素之间的药代动力学相互作用对协同延长大鼠同种异体心脏移植存活的影响。
影响因子：
6.2
作者：
Stepkowski,SM;Napoli,KL;Wang,ME;Qu,X;Chou,TC;Kahan,BD
通讯作者：
Kahan,BD
影响因子：
14.9
作者：
HOKE, GD;DRAPER, K;ECKER, DJ
通讯作者：
ECKER, DJ
影响因子：
4.4
作者：
Xian Chang Li;Prabir Roy-Chaudhury;Wayne W. Hancock;R. Manfro;Martin S. Zand;Yongsheng Li;X. Zheng;Peter W. Nickerson;Jürg Steiger;T. Malek;Terry B. Strom
通讯作者：
Xian Chang Li;Prabir Roy-Chaudhury;Wayne W. Hancock;R. Manfro;Martin S. Zand;Yongsheng Li;X. Zheng;Peter W. Nickerson;Jürg Steiger;T. Malek;Terry B. Strom