Liu Beixing, Zhang Leiying, Liu Jing, Shan Fengping, Wang Enhua, Kimura Yoshinobu
Department of Immunology, School of Basic Medical Science, China Medical University, Shenyang, PR China.
J Asthma. 2011 Nov;48(9):974-8. doi: 10.3109/02770903.2011.619288. Epub 2011 Oct 4.
Over 10% of entire population in Japan suffer from allergic diseases induced by Japanese cedar pollen (JCP) every spring. In terms of preventive medicine, it has become a matter of urgency to establish successful prophylactic and therapeutic strategies for controlling the disorders. The effect of an oligodeoxynucleotide containing a cytidine-guanosine motif (CpG ODN) on the regulation of immune responses induced by JCP was investigated in this study.
BALB/c mice were inoculated with CpG ODN intraperitoneally before intranasal sensitization to JCP. Cellular infiltration in the lung of BALB/c mice after treatment with CpG ODN or JCP was performed by hematoxylin and eosin (H&E) staining. Antibody titers and cytokines levels were determined by ELISA.
Intranasal inoculation of BALB/c mice with JCP induced a T-helper type 2 (Th2-type) dominant immune response, as characterized by the production of interleukin (IL)-4 and IL-5 in the lung and of JCP-specific IgE antibody in serum. Prior intraperitoneal administration of CpG ODN to mice suppressed the subsequent JCP-induced antibody production and infiltration of inflammatory cells in the lung. The inhibitory mechanism of CpG ODN seemed to be attributable to a CpG ODN-induced Th1-type dominant environment, which down-regulated Th2-type response subsequently induced by JCP allergen sensitization. Furthermore, administration with CpG ODN decreased the production of JCP-induced IL-17, which has been found to play a pivotal role in several inflammatory diseases including allergic asthma. The decreased production of IL-17, together with reduced secretion of IL-4 and IL-5, may contribute to diminish the inflammation in the lung of JCP-sensitized mice.
This work provides evidence that the CpG ODN has a prophylactic effect on the JCP-induced Th2-type allergic responses by establishing or restoring a Th1-type shift of immune environments.
每年春天，日本超过10%的人口患有由日本雪松花粉（JCP）引起的过敏性疾病。就预防医学而言，建立成功的预防和治疗策略以控制这些疾病已成为当务之急。本研究调查了含胞嘧啶-鸟嘌呤基序的寡脱氧核苷酸（CpG ODN）对JCP诱导的免疫反应调节的影响。
在对BALB/c小鼠进行JCP鼻内致敏之前，腹腔内接种CpG ODN。用苏木精和伊红（H&E）染色法观察CpG ODN或JCP处理后BALB/c小鼠肺组织中的细胞浸润情况。通过酶联免疫吸附测定（ELISA）法测定抗体滴度和细胞因子水平。
对BALB/c小鼠进行JCP鼻内接种可诱导以肺部产生白细胞介素（IL）-4和IL-5以及血清中产生JCP特异性IgE抗体为特征的2型辅助性T细胞（Th2型）主导的免疫反应。预先给小鼠腹腔注射CpG ODN可抑制随后JCP诱导的抗体产生以及肺部炎症细胞浸润。CpG ODN的抑制机制似乎归因于CpG ODN诱导的Th1型主导环境，该环境随后下调了JCP变应原致敏诱导的Th2型反应。此外，给予CpG ODN可降低JCP诱导的IL-17的产生，IL-17已被发现在包括过敏性哮喘在内的几种炎症性疾病中起关键作用。IL-17产生的减少，连同IL-4和IL-5分泌的减少，可能有助于减轻JCP致敏小鼠肺部的炎症。
本研究提供了证据表明，CpG ODN通过建立或恢复免疫环境的Th1型转变，对JCP诱导的Th2型过敏反应具有预防作用。
