Autocrine effects of interleukin-6 mediate acute-phase proinflammatory and tissue-reparative transcriptional responses of canine bladder mucosa.
Autocrine effects of interleukin-6 mediate acute-phase proinflammatory and tissue-reparative transcriptional responses of canine bladder mucosa.
复制标题
IL-6 的自分泌作用介导犬膀胱粘膜的急性期促炎和组织修复转录反应。
DOI：
10.1128/iai.01102-10
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发表时间：
2011
影响因子：
3.1
通讯作者：
Gookin,JodyL
中科院分区：
文献类型：
--
作者：
Wood,MichaelW;Breitschwerdt,EdwardB;Gookin,JodyL
During early urinary tract infection (UTI) the interplay between invading bacteria and the urothelium elicits a mucosal response aimed at clearing infection. Unfortunately, the resultant inflammation and associated local tissue injury are responsible for patient symptoms. Interleukin-6 (IL-6), a cytokine released during acute UTI, has both pro- and anti-inflammatory effects on other body systems. Within the urothelium, the IL-6 native-tissue origin, the target cell type(s), and ultimate effect of the cytokine on target cells are largely unknown. In the present study we modeled the UTI IL-6 responseex vivousing canine bladder mucosa mounted in Ussing chambers to determine the inflammatory and reparative role of IL-6. We demonstrated that uropathogenicEscherichia coliinfection stimulates the synthesis of IL-6 by all urothelial cell layers, with the urothelial cells alone representing the only site of unequivocal IL-6 receptor expression. Autocrine effects of IL-6 were supported by the activation of urothelial STAT3 signaling and SOCS3 expression. Using exogenous IL-6, a microarray approach, and quantitative reverse transcriptase PCR (q-RT-PCR), 5 target genes (tumor necrosis factor alpha, interleukin-1β, matrix metallopeptidase 2, heparan sulfated-glucosaminyl 3-O-sulfotransferase 3A1, and hyaluronan synthase 2) that have direct or indirect roles in promoting a proinflammatory state were identified. Two of these genes, heparan sulfated-glucosaminyl 3-O-sulfotransferase 3A1 and hyaluronan synthase 2, are also potentially important mediators of wound repair via the production of glycosaminoglycan components. These findings suggest that IL-6 secretion during acute UTI may serve a dual biological role by initiating the inflammatory response while also repairing urothelial defenses.
