Therapeutic effects of streptococcal preparation OK-432 on atopic dermatitis-like lesions in NC/Nga mice: possible shift from a Th2- to Th1-predominance
Therapeutic effects of streptococcal preparation OK-432 on atopic dermatitis-like lesions in NC/Nga mice: possible shift from a Th2- to Th1-predominance
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DOI：
10.1016/j.jdermsci.2004.06.006
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发表时间：
2004-09-01
影响因子：
4.6
通讯作者：
Nishioka, K
中科院分区：
文献类型：
--
作者：
Horiuchi, Y;Bae, S;Nishioka, K
背景资料：Th 1细胞介导的免疫反应的诱导（可能是通过细菌刺激引起的）可能有助于控制特应性皮炎（AD）等特应性疾病。链球菌制剂OK-432已显示出通过IL-12的作用而成为有效的Th 1诱导剂。NC/Nga小鼠在正常条件下可发生与人类AD相似的皮炎。目的：研究OK-432局部注射和/或皮下注射对NC/Nga小鼠AD样病变的治疗作用。用IL-4/IL-12 p40和CD 80/86以及磷酸化的STAT 4/p-STAT 6进行免疫组织化学染色，以及用RT-PCR检测IL-4/IL-12 p40和STAT 6/p-STAT 6。结果：在注射OK-432后5周，对于治疗NC/Nga小鼠的头部和背部病变，发现12只OK-432治疗的NC小鼠中有10只在临床上有相当大的改善。在OK-432处理的小鼠的头部和背部皮肤上，与未处理的小鼠相反，IL-12 p40/CD 80阳性细胞浸润是明显的。OK-432处理的小鼠中的IL-4/CD 86阳性细胞浸润比未处理的小鼠显著减少，并且OK-432处理的小鼠中几乎不存在IL-4 mRNA表达。结论：OK-432治疗可诱导NC/Nga小鼠AD样病变中Th 1细胞应答，下调Th 2细胞应答。目前的结果表明，来自这种链球菌的细菌组分可能构成治疗AD的有效的新治疗方法。(C)2004年日本皮肤病研究学会。由Elsevier爱尔兰有限公司出版。保留所有权利。
Background: The inducement of Th1 cell-mediated immune response, possibly brought about through bacterial stimulation, may serve to control atopic disorders such as atopic dermatitis (AD). The streptococcal preparation, OK-432, has been shown a potent Th1 inducer through the action of IL-12. NC/Nga mice under ordinary conditions have been found to contract dermatitis similar to human AD.Objective: Examination was made of the therapeutic effects of OK-432 local intra-and/or subcutaneous injections on AD-like lesions in NC/Nga mice.Methods: Immunohistochemical staining with IL-4/IL-12p40 and CD80/86 and phosphorylated STAT4/p-STAT6 and RT-PCR for IL-4/IL-12p40 and STAT6/STAT4 mRNA was conducted for the evaluation of OK-432 treatment of spontaneous AD-like lesions in NC/Nga mice.Results: At 5 weeks following injection of OK-432, for treating head and back lesions in NC/Nga mice, 10 of 12 OK-432 treated NC mice were found to have clinically improved quite considerably. On the head and back skin of OK-432 treated mice, IL-12p40/CD80 positive cellular infiltration was conspicuous, in contrast to non-treated mice. IL-4/CD86 positive cellular infiltrates in OK-432-treated mice had decreased significantly more than in non-treated mice and IL-4 mRNA expression was virtually absent in OK-432-treated mice. P-STAT4 positive cells could be seen abundantly present in OK-432-treated mice, and p-STAT6 positive cells were much fewer than in non-treated mice.Conclusions: OK-432-treatment appears to induce Th1 cellular response and to down-regulate that of the Th2 pathway in AD-like lesions of NC/Nga mice. The present results demonstrate bacterial components from such Streptococcus to likely constitute an effective new therapeutic approach in the treatment of AD. (C) 2004 Japanese Society for Investigative Dermatology. Published by Elsevier Ireland Ltd. All rights reserved.