Enhanced chemokine response in experimental acute Escherichia coli pyelonephritis in IL-1β-deficient mice
Enhanced chemokine response in experimental acute Escherichia coli pyelonephritis in IL-1β-deficient mice
复制标题
DOI：
10.1046/j.1365-2249.2003.02076.x
复制
发表时间：
2003-02-01
影响因子：
4.6
通讯作者：
Brauner, A
中科院分区：
文献类型：
--
作者：
Hertting, O;Khalil, A;Brauner, A
本研究的目的是研究IL-1 β和大肠杆菌对急性肾盂肾炎小鼠肾脏中MIP-2、MCP-1和RANTES的表达和分泌的影响。雌性Bki NMRI，以及IL-1 β缺陷小鼠和它们的野生型同窝小鼠，经尿道感染E. coliCFT 073或注射0.9%（w/v）NaCl后阻断6 h。在0、24、48 h和6 d处死Bki NMRI小鼠，在48 h处死IL-1 β缺陷小鼠。趋化因子的mRNA和蛋白水平在24小时达到峰值，测试趋化因子的mRNA表达定位于肾小管上皮细胞和MIP-2也在中性粒细胞。阻塞本身也诱导了类似于E.大肠杆菌感染，虽然在较低的水平。有趣的是，与野生型同窝出生的小鼠相比，IL-1 β缺陷小鼠的MIP-2水平更高。同样地，IL-1 β缺陷小鼠的炎症变化比野生型小鼠更频繁，并且当存在时，更广泛。用相同的细菌抗原刺激人肾小管上皮细胞系（HREC）A498和原代人肾小球系膜细胞（HMC），描述了相同趋化因子的基因表达。从两种细胞类型中观察到IL-8和MCP-1的快速释放。RANTES反应在HREC和HMC中均延迟。我们认为急性E.大肠杆菌肾盂肾炎诱导主要定位于上皮细胞的MIP-2/IL-8、MCP-1和RANTES表达和分泌，并且在用人上皮细胞和系膜细胞的相同细菌抗原体外刺激后证实了这种产生。因此，阻断趋化因子反应的诱导可能是可能的治疗干预的有吸引力的靶点。
The aim of the present study was to investigate the effects of IL-1beta and Escherichia coli on the expression and secretion of MIP-2, the mouse equivalent to human IL-8, MCP-1 and RANTES in the kidneys of mice with acute pyelonephritis. Female Bki NMRI, as well as IL-1beta deficient mice and their wild-type littermates, were transurethrally infected with either E. coli CFT 073 or injected with NaCl 0.9% (w/v) and thereafter obstructed for 6 h. The Bki NMRI mice were killed at 0, 24, 48 h and 6 days and the IL-1beta -deficient mice at 48 h. Chemokine mRNA and protein levels peaked at 24 h for the tested chemokines with the mRNA expression localized in the tubular epithelial cells and for MIP-2 also in neutrophils. Obstruction per se , also induced a chemokine expression similar to E. coli infection although at a lower level. Interestingly, MIP-2 levels were higher in the IL-1beta deficient mice as compared with the wild-type littermates. Likewise, the inflammatory changes were more frequent and, when present, more widespread in the IL-1beta -deficient mice than in the wild-type mice. Stimulation of a human renal tubular epithelial cell line (HREC), A498 and of primary human mesangial cells (HMC) with the same bacterial antigen depicted gene expression of the same chemokines. A rapid release of IL-8 and MCP-1 was observed from both cell types. RANTES response was delayed both in the HREC and the HMC. We conclude that acute E. coli pyelonephritis induces a MIP-2/IL-8, MCP-1 and RANTES expression and secretion localized primarily to the epithelial cells and that this production is confirmed after in vitro stimulation with the same bacterial antigen of human epithelial and mesangial cells. Blockade of induction of chemokine response may thus be an attractive target for possible therapeutic intervention.