Analysis of the intracellular signals regulating hyperosmolarity-and cooling-induced cytokine expression in bronchial epithelium

支气管上皮细胞内信号调节高渗透压和冷却诱导的细胞因子表达的分析

基本信息

批准号：
10670565
负责人：
HORIE Takashi
金额：
$ 2.05万
依托单位：
Nihon 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 2000
项目状态：
已结题

项目摘要

We examined the basic mechanism in the recruitment of eosinophils and neutrophils into the airway of exercise-induced asthma. To clarify these issues, we exposed airway epithelial cells (AEC) to hyperosmolar medium and cold medium, and IL-8 and RNATES in the culture supernatants were determined. We simultaneously examined the role of p38 MARK and JNK in cytokine production in response to hyperosmolarity and cooling. The results showed that hyperosmorality and cooling induced p38 MAPK and JNK activation and that a specific inhibitor of p38 MAPK and a specific inhibitor of JNK inhibited IL-8 and RANTES production by AEC in response to hyperosmolarity, and cooling and rewarming, indicating that p38 MAPK and JNK regulate IL-8 and RANTES production by AEC upon the environmental stresses including hyperosmolarity and low temperature. Finally, we examined the effect of inhalant corticosteroids on cytokine production in response to hyperosmolarity and cooling/rewarming. Inhalant corticosteroids inhibited cytokine production. Although it is not known, at this time, whether inhaled corticosteroids are capable of producing beneficial effect in preventing development of a LPR induced by exercise, our results may indicate that a strategy of inhibiting IL-8 and RANTES production may apply to preventing development of a LPR induced by exercise as well as reducing the allergic inflammation of asthmatic airway. In conclusion, the present study supported by grant-in-aid for scientific research clarified the basic mechanism in airway inflammation which might be occurred in EIA and a potential beneficial effect of inhalant corticosteroids in preventing development of a LPR induced by exercise.

我们检查了嗜酸性粒细胞和中性粒细胞募集到运动引起的哮喘气道中的基本机制。为了澄清这些问题，我们将气道上皮细胞（AEC）暴露于高质介质和冷培养基中，并确定了培养上清液中的IL-8和rnates。我们同时研究了P38 Mark和JNK在响应高渗透性和冷却中的细胞因子产生中的作用。结果表明，高渗透和冷却诱导p38 MAPK和JNK激活，并且p38 MAPK的特定抑制剂和JNK的特定抑制剂抑制了IL-8和AEC对高渗透性的产生，并响应高渗透性，以及冷却和重新恢复，表明P38 MAPK MAPK MAPK和JNK通过AEC调节IL-8，并在环境应力上产生包括高温和低温的环境应力。最后，我们检查了吸入糖皮质激素对响应高渗性和冷却/重新加热的细胞因子产生的影响。吸入性皮质类固醇抑制细胞因子的产生。尽管目前尚不清楚，但目前，吸入的皮质类固醇是否能够产生有益的效果来防止通过运动引起的LPR的发展，我们的结果可能表明，抑制IL-8和RANTES生产的策略可能适用于防止发展运动引起的LPR以及减少哮喘气道的过敏性炎症。总而言之，赠款支持科学研究的本研究阐明了EIA可能发生的气道炎症的基本机制，以及吸入性皮质类固醇在防止运动引起的LPR发展方面的潜在有益作用。