Pseudomonas aeruginosa Exoenzyme S Induces Transcriptional Expression of Proinflammatory Cytokines and Chemokines

Pseudomonas aeruginosa infection of cystic fibrosis patients causes lung damage that is substantially orchestrated by cytokines. In this study, multi-gene probe analysis was used to characterize the ability of the P. aeruginosa mitogen, exoenzyme S, to induce proinflammatory and immunoregulatory cytokines and chemokines. Exoenzyme S strongly induced transcription of proinflammatory cytokines and chemokines (tumor necrosis factor alpha, interleukin-1α [IL-1α], IL-1β, IL-6, IL-8, MIP-1α, MIP-1β, MCP-1, RANTES, and I-309), modest transcription of immunoregulatory cytokines (IL-10 and IL-12p40), and weak transcription of Th1 cytokines (IL-2 and gamma interferon). The response occurred early and subsided without evolving over time. These data suggest that cells responding to exoenzyme S would rapidly express proinflammatory cytokines and chemokines that may contribute to pulmonary inflammation in cystic fibrosis.

囊性纤维化（cystic fibrosis）患者感染铜绿假单胞菌（Pseudomonas aeruginosa）后引发的肺损伤，在很大程度上由细胞因子主导调控。本研究采用多基因探针分析（multi-gene probe analysis）技术，对铜绿假单胞菌促分裂原外酶S（exoenzyme S）诱导促炎细胞因子（proinflammatory cytokines）、免疫调节细胞因子（immunoregulatory cytokines）及趋化因子（chemokines）的能力进行了表征。外酶S可强力诱导促炎细胞因子与趋化因子的转录，包括肿瘤坏死因子α（tumor necrosis factor alpha）、白细胞介素-1α（IL-1α）、IL-1β、IL-6、IL-8、巨噬细胞炎症蛋白-1α（MIP-1α）、巨噬细胞炎症蛋白-1β（MIP-1β）、单核细胞趋化蛋白-1（MCP-1）、正常T细胞表达和分泌激活调节因子（RANTES）以及I-309；对免疫调节细胞因子（IL-10与IL-12p40）的转录诱导作用中等；对Th1细胞因子（Th1 cytokines）中的IL-2及γ干扰素（gamma interferon）的转录诱导作用较弱。该应答发生较早，且随时间推移未出现进展便逐渐消退。上述数据表明，对外酶S产生应答的细胞可快速表达促炎细胞因子与趋化因子，这可能参与介导囊性纤维化患者的肺部炎症反应。