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Establishment of animal models for atopic dermatitis and induction of oral tolerance

特应性皮炎动物模型的建立及口服耐受的诱导

基本信息

批准号：
08670982
负责人：
HAYAKAWA Kazuhito
金额：
$ 1.41万
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：
1996
资助国家：
日本
起止时间：
1996 至 1997
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-08670982/
关键词：
atopic dermatitis animal model oral tolerance cytokine mRNA RT-PCR method in situ hybridization in situハイブリダイゼーション

项目摘要

BALB/C mice were sensitized with 2,4,6-trinitro-chlorobenz ine, and then were repeatedly elicited on the original sensitized site with the same antigen at 2-day intervals for 24 days. To investigate the differences in the cutaneous cytokine milieu between the acute and chronic phases of contact hypersensitivity, sequential cytokine dynamics after 2,4,6-trinitro-chlorobenzine application were assessed in the acute vs chronic lesions, using RT-PCR technique. As a result, increased mRNA levels for Th1-type cytokines (IL-2, IFN-gamma) were observed in the acute lesions, whereas those for Th2-type cytokines (IL-4, IL-10) were markedly up-regulated in the chronic lesions.Similar study with BALB/C mice sensitized by subcutaneous nickel injection also showed that repeated applications of nickel gave rise to a shift from Th1 to Th2 dominated responses. Oral administration of nickel prior to repeated elicitation suppressed development of dermatitis. We demonstrated Th2-type responses in the repeatedly elicited sites, using RT-PCR technique.Subsequently, BALB/C mice were sensitized with 2,4,6-trinitro-chlorobenzine and then were repeatedly elicited on the original sensitized site with the same antigen at 2-day intervals for 24 days. Using in-situ hybridization technique, we examined time course and localization of expression for IFN-gamma mRNA and IL-10mRNA.In the acute lesions, we demonstrated increased expression for IFN-gamma mRNA on T cells in the dermis between several and 12 hours. Expression of IL-10mRNA on T cells in the dermis was up-regulated between 10 and 24 hours. In the chronic lesions, expression of IL-10mRNA was observed on infiltrating T cells into epidermis and dermis at 3-24 hours.

用2，4，6-三硝基氯苯致敏BALB/C小鼠，然后在原致敏部位用同一抗原重复激发，间隔2天，共24天。为了研究接触性超敏反应急性期和慢性期皮肤细胞因子环境的差异，使用RT-PCR技术评估了2，4，6-三硝基氯苯应用后急性和慢性病变中细胞因子动态的变化。结果表明，在急性损伤中，Th 1型细胞因子（IL-2，IFN-γ）的mRNA水平显著升高，而在慢性损伤中，Th 2型细胞因子（IL-4，IL-10）的mRNA水平显著升高。在反复诱发之前口服镍抑制皮炎的发展。用2，4，6-三硝基氯苯致敏BALB/C小鼠，然后在原致敏部位用相同抗原重复激发，间隔2d，共24 d。采用原位杂交技术检测IFN-γ mRNA和IL-10 mRNA表达的时间过程和定位。真皮T细胞IL-10 mRNA表达在10 ~ 24 h之间上调。在慢性病变中，在3-24小时，在表皮和真皮中的浸润T细胞上观察到IL-10 mRNA的表达。