权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

SUPPRESSION OF EXPERIMENTAL AUTOIMMUNE UVEORETINITIS BY NEUROPEPTIDE GENE-TRANSFECT-CELLS

神经肽基因转染细胞抑制实验性自身免疫性葡萄膜视网膜炎

基本信息

批准号：
17591855
负责人：
KEZUKA Takeshi
金额：
$ 2.3万
依托单位：
TOKYO MEDICAL UNIVERSITY
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2005
资助国家：
日本
起止时间：
2005 至 2006
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-17591855/
关键词：
CGRP UVEITIS GENE THERAPY DENDRITIC CELL

项目摘要

To investigate the role of the suppression in murine experimental autoimmune uveoretinitis (EAU) by mature dendritic cells (DC) cultured with calcitonin gene-related peptide (CGRP). Bone marrow cells derived from C57BL/6 mice were cultured with GM-CSF for six days, and differentiated CD11^+ immature DC were purified by autoMACS. Immature DC were further cultured with LPS (1 μg/ml) overnight, and then with human interphotoreceptor retinoid binding protein (IRBP) residues 1-20 (hIRBP-p) in the presence of CGRP or TGF-B2. EAU was induced by immunization with hIRBP-p in Freund' s adjuvant and pertussis toxin in mice. At the same time, hIRBP-p-immunized mice were injected the mature DC cultured with CGRP or TGF-B2 intravenously. On day 19 after immunization, hIRBP-p-specific delayed hypersensitivity (DH) were measured. On day 21 after immunization, animals were sacrificed, and assessed the extent of EAU pathologically. EAU and antigen-specific DH was predominantly suppressed by injection of mature DC cultured with CGRP or TGF-B2 and hIRBP-p. Incidence of EAU on control group was 87% (13 of 15 EAU mice), TGF-B2 culture group was 60% (9 of 15 EAU mice), and CGRP culture group was 28% (5 of 18 EAU mice). On the next experiments, we prepared CGRP gene-transfect-DC by electroporation methods. As the results, CGRP gene-transfect-DC can suppress EAU, and suppress DH spepific for IRBP-p. It was demonstrated that mature DC cultured with CGRP and CGRP gene-transfect-DC play an immunosuppressive role in development of EAU, which were more effective than those cultured with TGF-B2.

目的探讨降钙素基因相关肽（CGRP）诱导的成熟树突状细胞（DC）对小鼠实验性自身免疫性葡萄膜视网膜炎（EAU）的抑制作用。将C57 BL/6小鼠的骨髓细胞与GM-CSF培养6天，用autoMACS纯化分化的CD 11 ^+未成熟DC。将未成熟DC与LPS（1 μg/ml）进一步培养过夜，然后在CGRP或TGF-β 2存在下与人光感受器间类视黄醇结合蛋白（IRBP）残基1-20（hIRBP-p）培养。通过用在弗氏佐剂中的hIRBP-p和百日咳毒素在小鼠中免疫诱导EAU。同时，将CGRP或TGF-β 2诱导的成熟DC静脉注射hIRBP-p免疫小鼠。在免疫后第19天，测量hIRBP-p特异性迟发型超敏反应（DH）。在免疫后第21天，处死动物，并对EAU的程度进行病理学评估。对照组EAU发生率为87%（13/15），TGF-B2培养组为60%（9/15），CGRP培养组为28%（5/18）。在接下来的实验中，我们采用电穿孔法制备了CGRP基因转染DC。结果表明，CGRP基因-β-DC能抑制EAU的发生，并能抑制IRBP-p特异性的DH，证明CGRP和CGRP基因-β-DC对EAU的发生具有免疫抑制作用，其作用优于TGF-β_2。

项目成果

期刊论文数量（10）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Possibility of inducing anterior chamber-associated immune deviation by TGF-β2 treatment of monocytes isolated from Behcets patients.

通过 TGF-β2 处理从 Behcets 患者分离的单核细胞诱导前房相关免疫偏差的可能性。

DOI：
发表时间：
2006
期刊：
Exp Eye Res 83
影响因子：
0
作者：
Takeuchi M.;Keino H.;Suzuki J.;Usui Y.;Hattori T.;Takeuchi A.;Oh-i K.;Okunuki Y.;Kezuka T.;Usui M.
通讯作者：
Usui M.

Intravitoreal injection of Tacrolimus (FK506) suppresses ongoing experimental autoimmune uveoretinitis in rats.

玻璃体内注射他克莫司 (FK506) 可抑制大鼠正在进行的实验性自身免疫性葡萄膜视网膜炎。

DOI：
发表时间：
2007
期刊：
Br J Ophthalmol 91
影响因子：
0
作者：
Oh-i K.;Keino H.;Goto H.;Yamakawa N.;Murase K.;Usui Y.;Kezuka T.;Sakai J.;Takeuchi M.;Usui M.
通讯作者：
Usui M.

Acute retinal necrosis.Immune Response and the Eye. Chem Immunol Allergy 92(Niederkorn JY, Kaplan HJ (eds))

急性视网膜坏死。免疫反应和眼睛。

DOI：
发表时间：
2007
期刊：
影响因子：
0
作者：
Kezuka T.;Atherton SS.(分担執筆)
通讯作者：
Atherton SS.(分担執筆)

The role of the ICOS/B7RP‐1 T cell costimulatory pathway in murine experimental autoimmune uveoretinitis

DOI：
10.1002/eji.200636138
发表时间：
2006-11
期刊：
European Journal of Immunology
影响因子：
5.4
作者：
Y. Usui;H. Akiba;M. Takeuchi;T. Kezuka;A. Takeuchi;T. Hattori;Y. Okunuki;Tomohide Yamazaki;H. Yagita;M. Usui;K. Okumura
通讯作者：
Y. Usui;H. Akiba;M. Takeuchi;T. Kezuka;A. Takeuchi;T. Hattori;Y. Okunuki;Tomohide Yamazaki;H. Yagita;M. Usui;K. Okumura

Kaplan HJ (eds) : Immune Response and the Eye.

Kaplan HJ（编辑）：免疫反应和眼睛。