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Establishment of animal models reflecting heterogeneity in atopic dermatitis

反映特应性皮炎异质性的动物模型的建立

基本信息

批准号：
10670803
负责人：
HAYAKAWA Kazuhito
金额：
$ 1.86万
依托单位：
Kyorin University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
1998
资助国家：
日本
起止时间：
1998 至 1999
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-10670803/
关键词：
atopic dermatitis animal model BALB c C57BL 6 TH1 TH2 cytokine draining lymph node cells アトーピー性皮膚炎 OX Th1 Th2

项目摘要

BALB/c and C57BL/6 mice were sensitized by the application of OX solutions to the ear, then were repeatedly elicited on the original sensitized site with the same antigen. Hapten-specific ear swelling reaction was shifted from delayed hypersensitivity to early-type of the late phase reaction in both strains. Only BALB/c mice showed a remarkable immediate reaction 30 min after the application of the hapten. IgE production was demonstrated in BALB/c mice, whereas it was not in C57BL/c mice.Sequential cytokine dynamics after OX application were assessed in the acute and chronic phases with RT-PCR technique, using samples taken from the skin and draining lymph nodes. In BALB/c mice, increased mRNA levels for both TィイD2HィエD21 and TィイD2HィエD22-type cytokines were observed in the acute phase, and those for TィイD2HィエD22-type cytokines were up-regulated in the chronic phase. Whereas, in C57BL/6 mice, there were increased mRNA levels for only TィイD2HィエD21-type cytokines in the acute phase. In the chronic phase, like BALB/c mice, mRNA levels for the TィイD2HィエD22-type cytokines were up-regulated.Subsequently, we studied the cytokine patterns in the acute and chronic phases by measurement of cytokine production (IFN-γ, IL-4, IL-10) with ELISA technique, using ear skin and draining lymph nodes of BALB/c and C57BL/6 mice. As a result, both strains showed that TィイD2HィエD22 cytokines become to be dominant with changing from the acute to chronic phase. There is no significant difference in the ratio of TィイD2HィエD21 to TィイD2HィエD22 cytokines in the chronic phase between two strains.. These results indicate that there is a shift from TィイD2HィエD21 to TィイD2HィエD22 response regardless of mouse strains, when contact dermatitis becomes to be chronic, This reaction may play an important role in maintaining homeostasis by reducing cytotoic TィイD2HィエD21 reaction.

BALB/c和C57 BL/6小鼠用OX溶液致敏，然后在原始致敏部位用相同的抗原重复激发。半抗原特异性耳肿胀反应由迟发型超敏反应转变为迟发型反应的早期型。只有BALB/c小鼠在应用半抗原后30分钟显示出显著的立即反应。BALB/c小鼠中证实了IgE的产生，而C57 BL/c小鼠中则没有。使用从皮肤和引流淋巴结采集的样品，用RT-PCR技术评估了OX应用后急性和慢性阶段的细胞因子动态。在BALB/c小鼠中，在急性期观察到T细胞D2 H受体D21和T细胞D2 H受体D22型细胞因子的mRNA水平增加，在慢性期观察到T细胞D2 H受体D22型细胞因子的mRNA水平上调。而在C57 BL/6小鼠中，在急性期仅T细胞D2 H受体D21型细胞因子的mRNA水平增加。在慢性期，与BALB/c小鼠一样，T淋巴细胞D2 H受体D22型细胞因子的mRNA水平上调。随后，我们通过ELISA技术检测BALB/c和C57 BL/6小鼠耳皮肤和引流淋巴结中细胞因子（IFN-γ，IL-4，IL-10）的产生，研究了急性期和慢性期细胞因子的模式。结果表明，从急性期到慢性期，两种菌株都显示T细胞D2 H和D22细胞因子成为优势。在慢性期，两株之间的T细胞D2 H细胞D21与T细胞D2 H细胞D22细胞因子的比率没有显著差异。这些结果表明，无论小鼠品系如何，当接触性皮炎变成慢性时，都会从TイD2 H D21反应转变为TイD2 H D22反应，该反应可能通过减少细胞毒性TイD2 H D21反应在维持体内平衡方面发挥重要作用。