Regulation of cyclooxygenase-2 expression in human bladder epithelial cells infected with type I fimbriated uropathogenic E. coli
Regulation of cyclooxygenase-2 expression in human bladder epithelial cells infected with type I fimbriated uropathogenic E. coli
复制标题
DOI：
10.1111/j.1462-5822.2011.01650.x
复制
发表时间：
2011-11-01
影响因子：
3.4
通讯作者：
Chen, Cheng-Nan
中科院分区：
文献类型：
--
作者：
Chen, Te-Chuan;Tsai, Jen-Pi;Chen, Cheng-Nan
尿路致病性大肠埃希菌(UPEC)1型菌毛在膀胱炎和尿路感染(UTI)的发病机制中起重要作用。随着感染和炎症过程，包括尿路感染，尿前列腺素(PG)水平和尿颗粒中环氧合酶(COX)-2的表达可能增加。我们研究了1型菌毛UPEC株J96(J96-1)侵袭人膀胱5637细胞对COX-2表达的调控机制。膀胱5637细胞感染J96-1后，COX-2表达增加，PGE2分泌增加。通过使用特定的抑制剂和短发夹状RNA(ShRNA)，我们已经证明细胞外信号相关激酶(ERK)、c-Jun-NH2末端激酶(JNK)和p38 MAPK通路的激活在J96-1诱导的COX-2表达中起关键作用。荧光素酶报告和染色质免疫沉淀分析表明，J96-1的侵袭增加了5637细胞的核因子-B-和AP-1-DNA结合活性。抑制核因子？B和AP-1的激活可阻断J96-1诱导的COX-2启动子的活性和表达。J96-1对5637细胞信号转导和COX-2表达的影响是通过Toll样受体(TLR)-4介导的。综上所述，我们的发现提供了在5637细胞中1型转录因子J96依赖的COX-2表达的分子途径，为深入了解UPEC在膀胱上皮细胞侵袭中的作用提供了线索。
The type 1 fimbriae of uropathogenic Escherichia coli (UPEC) have been described as important for the establishment of bladder infections and urinary tract infections (UTI). Urinary prostaglandin (PG) levels and cyclooxygenase (COX)-2 expression in urine particulates may increase with infectious and inflammatory processes, including UTIs. We investigated the mechanisms underlying the modulation of COX-2 expression through the invasion of type 1 fimbriated UPEC strain J96 (J96-1) in human bladder 5637 cells. Bladder 5637 cells infected with J96-1 induced increases in the expression of COX-2 and secretion of PGE2. By using specific inhibitors and short hairpin RNA (shRNA), we have demonstrated that the activation of extracellular signal-related kinase (ERK), c-Jun-NH2-terminal kinase (JNK) and p38 MAPK pathways is critical for J96-1-induced COX-2 expression. Luciferase reporters and chromatin immunoprecipitation assays suggest that J96-1 invasion increases NF-?B- and AP-1-DNA-binding activities in 5637 cells. Inhibition of NF-?B and AP-1 activations blocked the J96-1-induced COX-2 promoter activity and expression. The effect of J96-1 on 5637 cell signalling and COX-2 expression is mediated by Toll-like receptor (TLR)-4. In summary, our findings provide the molecular pathways underlying type 1 fimbriated J96-dependent COX-2 expression in 5637 cells, providing insight into the function of UPEC invasion in bladder epithelial cells.