Y27, a novel derivative of 4-hydroxyquinoline-3-formamide, prevents the development of murine systemic lupus erythematosus-like diseases in MRL/lpr autoimmune mice and BDF1 hybrid mice.
Y27, a novel derivative of 4-hydroxyquinoline-3-formamide, prevents the development of murine systemic lupus erythematosus-like diseases in MRL/lpr autoimmune mice and BDF1 hybrid mice.
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Y27 是 4-羟基喹啉-3-甲酰胺的新型衍生物，可预防 MRL/lpr 自身免疫小鼠和 BDF1 杂交小鼠患系统性红斑狼疮样疾病
DOI：
10.1186/ar4078
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发表时间：
2012-11-01
影响因子：
4.9
通讯作者：
Yun LH
中科院分区：
文献类型：
--
作者：
Xiao ZY;Chen SH;Cheng JP;Zhou WX;Zhang YX;Yang RF;Yun LH
天然存在的CD 4 + CD 25+调节性T细胞（Treg）是维持外周免疫耐受的关键。这些细胞的活性受损和/或频率降低导致系统性红斑狼疮（SLE）。调控Treg细胞的数量或活性是治疗自身免疫性疾病和其他自身免疫性疾病的一个有前途的策略。我们研究了一种新的4-羟基喹啉-3-甲酰胺衍生物Y27对MRL/lprautoimmune小鼠和BDF 1杂交小鼠SLE样症状的影响。Y27的有益作用是否涉及CD 4 + CD 25 +Treg细胞的调节也被investigated.MethodsFemale MRL/lpr小鼠自发发展狼疮口服治疗管饲法与Y27为10周，开始在10周龄。BDF 1小鼠通过每周两次静脉注射亲代雌性DBA/2脾淋巴细胞发生慢性移植物抗宿主病（GVHD），其特征为类似SLE的免疫复合物介导的肾小球肾炎。将Y27给予慢性GVHD小鼠12周。监测肾病症状，采用小鼠调节性T细胞染色试剂盒，流式细胞术检测外周血白细胞中CD 4 + CD 25 + FoxP 3 +Treg细胞百分比。纯化的CD 4 + CD 25 + T淋巴细胞的免疫抑制活性进行了评估，使用混合淋巴细胞reaction.ResultsThe MRL/lpr小鼠的寿命与Y27治疗10周显着延长，蛋白尿和肾脏病变的严重程度得到改善，血尿素氮，甘油三酯和血清抗双链DNA抗体下降。在慢性GVHD小鼠中发现了类似的结果。给予Y27对两组小鼠外周血淋巴细胞CD 4 + CD 25 + Foxp 3 +Treg细胞的百分比几乎没有影响。与此相反，Y27处理的小鼠脾细胞中CD 4 + CD 25 +Treg细胞的抑制能力明显增强。结论Y27对自身免疫性肾炎具有保护作用。其机制可能与增强CD 4 + CD 25 +Treg细胞的抑制能力有关。
IntroductionNaturally occurring CD4+CD25+regulatory T (Treg) cells are central to the maintenance of peripheral tolerance. Impaired activity and/or a lower frequency of these cells lead to systemic lupus erythematosus (SLE). Manipulating the number or activity of Treg cells is to be a promising strategy in treating it and other autoimmune diseases. We have examined the effects of Y27, a novel derivative of 4-hydroxyquinoline-3-formamide, on SLE-like symptoms in MRL/lprautoimmune mice and BDF1 hybrid mice. Whether the beneficial effect of Y27 involves modulation of CD4+CD25+Treg cells has also been investigated.MethodsFemale MRL/lprmice that spontaneously develop lupus were treated orally by gavage with Y27 for 10 weeks, starting at 10 weeks of age. BDF1 mice developed a chronic graft-versus-host disease (GVHD) by two weekly intravenous injections of parental female DBA/2 splenic lymphocytes, characterized by immunocomplex-mediated glomerulonephritis resembling SLE. Y27 was administered to chronic GVHD mice for 12 weeks. Nephritic symptoms were monitored and the percentage of CD4+CD25+FoxP3+Treg peripheral blood leukocyte was detected with mouse regulatory T cell staining kit by flowcytometry. Purified CD4+CD25+Tregs were assessed for immune suppressive activity using the mixed lymphocyte reaction.ResultsThe life-span of MRL/lpr mice treated with Y27 for 10 weeks was significantly prolonged, proteinuria and renal lesion severity were ameliorated, and blood urea nitrogen, triglyceride and serum anti-double-stranded DNA antibodies were decreased. Similar results were found in chronic GVHD mice. Administration of Y27 had little impact on percentage of the peripheral blood lymphocyte CD4+CD25+Foxp3+Treg cells in both groups of mice. In contrast, the suppressive capacity of CD4+CD25+Treg cells in splenocytes was markedly augmented in Y27-treated miceex vivo.ConclusionsExperimental evidence of the protect effects of Y27 against autoimmune nephritis has been shown. The mechanism may involve enhancement of the suppressive capacity of CD4+CD25+Treg cells.
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肝细胞生长因子在慢性移植物与宿主病的鼠狼疮模型中阻止狼疮肾炎。
影响因子：
4.9
作者：
Kuroiwa T;Iwasaki T;Imado T;Sekiguchi M;Fujimoto J;Sano H
通讯作者：
Sano H
影响因子：
168.9
作者：
Comi, G.;Pulizzi, A.;Filippi, M.
通讯作者：
Filippi, M.
影响因子：
4.3
作者：
Jones, SC;Murphy, GF;Korngold, R
通讯作者：
Korngold, R
DOI：
10.1073/pnas.0408197102
发表时间：
2005-01-11
影响因子：
11.1
作者：
Chen, ML;Pittet, MJ;Khazaie, K
通讯作者：
Khazaie, K
影响因子：
--
作者：
Okamoto A;Fujio K;Okamura T;Yamamoto K
通讯作者：
Yamamoto K