...
  • 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Infection and immunity >Suppressed Induction of Proinflammatory Cytokines by a Unique Metabolite Produced by Vibrio cholerae O1 El Tor Biotype in Cultured Host Cells
【24h】

Suppressed Induction of Proinflammatory Cytokines by a Unique Metabolite Produced by Vibrio cholerae O1 El Tor Biotype in Cultured Host Cells

机译：霍乱弧菌O1 El Tor生物型产生的独特代谢产物在培养的宿主细胞中抑制促炎细胞因子的诱导

获取原文
           
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

Vibrio cholerae O1 has two biotypes, El Tor and Classical, and the latter is now presumed to be extinct in nature. Under carbohydrate-rich growth conditions, El Tor biotype strains produce the neutral fermentation end product 2,3-butanediol (2,3-BD), which prevents accumulation of organic acids from mixed acid fermentation and thus avoids a lethal decrease in the medium pH, while the Classical biotype strains fail to do the same. In this study, we investigated the inhibitory effect of 2,3-BD on the production of two proinflammatory biomarkers, intreleukin-8 (IL-8) and tumor necrosis factor alpha (TNF-α), in human intestinal epithelial HT29 and alveolar epithelial A549 cells. Cell-free culture supernatants of El Tor strain N16961 grown in LB supplemented with 1% glucose induced a negligible amount of IL-8 or TNF-α, while the Classical O395 strain induced much higher levels of these proinflammatory cytokines. On the other hand, three mutant strains constructed from the N16961 strain with defects in the constitutive 2,3-BD pathway were also able to induce high levels of cytokines. When HT29 and A549 cells were treated with bacterial flagella, known proinflammatory cytokine inducers, and chemically synthesized 2,3-BD at various concentrations, a dose-dependent decrease in IL-8 and TNF-α production was observed, demonstrating the suppressive effect of 2,3-BD on the production of proinflammatory cytokines in epithelial cells. Upon cotreatment with extraneous 2,3-BD, elevated levels of IκBα, the inhibitor of the NF-κB pathway, were detected in both HT29 and A549 cells. Furthermore, treatments containing 2,3-BD elicited lower levels of NF-κB-responsive luciferase activity, demonstrating that the reduced cytokine production is likely through the inhibition of the NF-κB pathway. These results reveal a novel and potential role of 2,3-BD as an immune modulator that might have conferred a superior pathogenic potential of the El Tor over the Classical biotype.
机译：霍乱弧菌O1有两种生物型，埃尔托（El Tor）和古典型，现在假定后者已绝种。在富含碳水化合物的生长条件下，El Tor生物型菌株可产生中性发酵最终产物2,3-丁二醇（2,3-BD），可防止混合酸发酵中有机酸的积累，从而避免培养基pH值的致命降低。 ，而经典生物型菌株却无法做到这一点。在这项研究中，我们研究了2,3-BD对人肠道上皮HT29和肺泡上皮中两种促炎生物标记物intreleukin-8（IL-8）和肿瘤坏死因子α（TNF-α）的抑制作用。 A549细胞。在补充了1％葡萄糖的LB中生长的El Tor菌株N16961的无细胞培养上清液诱导的IL-8或TNF-α量可忽略不计，而Classic O395菌株诱导的促炎细胞因子水平更高。另一方面，由N16961菌株构建的3个突变型菌株在组成型2,3-BD途径中存在缺陷，也能够诱导高水平的细胞因子。当用细菌鞭毛，已知的促炎细胞因子诱导剂处理HT29和A549细胞并化学合成各种浓度的2,3-BD时，观察到IL-8和TNF-α的产生呈剂量依赖性降低，证明了其抑制作用。 2,3-BD对上皮细胞中促炎细胞因子的产生。与外源性2,3-BD共处理后，在HT29和A549细胞中均检测到升高的IκBα（NF-κB途径的抑制剂）水平。此外，含2,3-BD的治疗引起较低水平的NF-κB响应荧光素酶活性，表明减少的细胞因子产生可能是通过抑制NF-κB途径。这些结果揭示了2，3-BD作为免疫调节剂的新的和潜在的作用，其可能赋予了El Tor优于经典生物型的致病潜力。

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

客服邮箱：kefu@zhangqiaokeyan.com

京公网安备：11010802029741号 ICP备案号：京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有

  • 客服微信

  • 服务号