Broad up-regulation of innate defense factors during acute cholera
Broad up-regulation of innate defense factors during acute cholera
复制标题
DOI：
10.1128/iai.01900-06
复制
发表时间：
2007-05-01
影响因子：
3.1
通讯作者：
Holmgren, Jan
中科院分区：
文献类型：
--
作者：
Flach, Carl-Fredrik;Qadri, Firdausi;Holmgren, Jan
我们使用全基因组微阵列筛查系统（覆盖 47,000 个不同转录本的 Affymetrix 人类基因芯片）来检查急性霍乱期间十二指肠粘膜的基因表达。在腹泻发作后 2 天和 30 天，对 7 名霍乱患者的十二指肠粘膜进行活检，并两两比较急性期和恢复期样本中的基因表达模式。在肠上皮中表达的约 21,000 个转录本中，29 个被定义为在急性霍乱期间上调的转录本，33 个被定义为下调的转录本。大多数上调基因被发现在抵抗感染的先天防御中具有确定的或可能的作用；这些基因包括 LPLUNC1、LF、VCC1、TCN1、CD55、SERPINA3、MMP1、MMP3、IL1B、LCN2、SOCS3、GDF15、SLPI、CXCL13 和 MUC1 基因。验证性PCR的结果与微阵列数据很好地相关。免疫组织化学分析显示，急性霍乱期间，固有层细胞中乳铁蛋白的表达增加，上皮细胞中 CD55 的表达增加，而固有层和上皮细胞中 SERPINA3 蛋白（α(1)-抗胰凝乳蛋白酶）的表达增加。霍乱毒素（CT）刺激的Caco-2细胞中CD55和SERPINA3的表达模式与急性霍乱期间肠粘膜中发现的模式相同，表明肠上皮中CD55和SERPINA3基因的激活是由CT诱导的。总之，在急性霍乱感染期间，先天防御机制的开启程度以前未曾描述过。 CT 对上皮细胞的直接影响和固有层细胞的变化都有助于这种上调。
We used a whole-genome microarray screening system (Affymetrix human GeneChips covering 47,000 different transcripts) to examine the gene expression in duodenal mucosa during acute cholera. Biopsies were taken from the duodenal mucosa of seven cholera patients 2 and 30 days after the onset of diarrhea, and the gene expression patterns in the acute- and convalescent-phase samples were compared pairwise. Of about 21,000 transcripts expressed in the intestinal epithelium, 29 were defined as transcripts that were up-regulated and 33 were defined as transcripts that were down-regulated during acute cholera. The majority of the up-regulated genes characterized were found to have an established or possible role in the innate defense against infections; these genes included the LPLUNC1, LF, VCC1, TCN1, CD55, SERPINA3, MMP1, MMP3, IL1B, LCN2, SOCS3, GDF15, SLPI, CXCL13, and MUC1 genes. The results of confirmative PCR correlated well with the microarray data. An immunohistochemical analysis revealed increased expression of lactoferrin in lamina propria cells and increased expression of CD55 in epithelial cells, whereas increased expression of the SERPINA3 protein (alpha(1)-antichymotrypsin) was detected in both lamina propria and epithelial cells during acute cholera. The expression pattern of CD55 and SERPINA3 in cholera toxin (CT)-stimulated Caco-2 cells was the same as the pattern found in the intestinal mucosa during acute cholera, indicating that the activation of the CD55 and SERPINA3 genes in intestinal epithelium was induced by CT. In conclusion, during acute cholera infection, innate defense mechanisms are switched on to an extent not described previously. Both direct effects of CT on the epithelial cells and changes in the lamina propria cells contribute to this up-regulation.