Involvement of the cAMP-dependent signal transduction pathways in the mucosal adjuvant activity by bacterial diarrheal toxin

cAMP依赖性信号转导途径参与细菌性腹泻毒素的粘膜佐剂活性

• 批准号: 21790429
• 负责人: ARIMITSU Hideyuki
• 金额: $ 2.33万
• 依托单位: Fujita Health University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Young Scientists (B)
• 财政年份: 2009
• 资助国家: 日本
• 起止时间: 2009 至 2010
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-21790429/
• 关键词: シグナル伝達; 粘膜免疫; cAMP; 下痢毒素; アジュバント; 細菌下痢毒素; コレラ毒素; CREB; 粘膜アジュバント; 毒素原性大腸菌易熱性毒素

In order to analyze the involvement of cAMP in mucosal adjuvant activity induced by cholera toxin (CT) in molecular biological level, various assays were employed by using the CT, its mutant CT(E112Q) and the B subunit (CTB). The CT bound to the splenocytes through the interaction between CTB and GM1, followed by the activation of the PKA-CREB pathway which was downstream signal of cAMP and p38-CREB pathways, dependent on the enzymatic activity of the A subunit. Furthermore, the splenocytes, which were prepared from mice which were administered intranasally with the CT, produced cytokines in response to the stimulation from the CT and E112Q. These activities were neither found in the splenocytes nor the mice treated with E112Q and CTB, indicating that the cAMP-dependent signal transduction induced by the activity of the CT involves some adjuvant activities.

为了从分子生物学水平上分析cAMP参与霍乱毒素（CT）诱导的粘膜佐剂活性，本研究以CT及其突变体CT（E112 Q）和B亚基（CT B）为研究对象，进行了多种实验研究。CT通过CTB与GM 1的相互作用与脾细胞结合，继而激活cAMP和p38-CREB通路的下游信号PKA-CREB通路，依赖于A亚基的酶活性。此外，从鼻内施用CT的小鼠制备的脾细胞响应于来自CT和E112 Q的刺激而产生细胞因子。这些活性在脾细胞和用E112 Q和CTB处理的小鼠中均未发现，表明由CT活性诱导的cAMP依赖性信号转导涉及一些佐剂活性。

项目成果

Molecular Analysis of an Extrachromosomal Element Containing the C2 Toxin Gene Discovered in Clostridium botulinum Type C

C 型肉毒杆菌中发现的含有 C2 毒素基因的染色体外元件的分子分析

• 发表时间: 2009
• 期刊: Journal of Bacteriology
• 影响因子: 3.2
• 作者: Y. Sakaguchi;Tetsuya Hayashi;Yumiko Yamamoto;K. Nakayama;Kai Zhang;Shaobo Ma;H. Arimitsu;K. Oguma
• 通讯作者: K. Oguma