Interleukin-8 is essential for normal urothelial cell survival
Interleukin-8 is essential for normal urothelial cell survival
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DOI：
10.1152/ajprenal.90733.2008
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发表时间：
2009-09-01
影响因子：
4.2
通讯作者：
Liebert, Monica
中科院分区：
文献类型：
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作者：
Tseng-Rogenski, Stephanie;Liebert, Monica
放大图片创作者：Tseng-Rogenski S，Liebert M.白细胞介素-8对正常尿路上皮细胞存活至关重要。美国肾脏生理学杂志297：F816-F821，2009年。首次发表于2009年6月17日; doi：10.1152/ajprenal.90733.2008。白细胞介素-8（IL-8; CXCL 8）已被证明在多种细胞过程中发挥作用。在这里，我们报告了IL-8作为正常人尿路上皮细胞的生长和基本生存因子的额外作用。向正常尿路上皮细胞补充外源性重组人IL-8通过Akt途径促进细胞生长。通过小抑制RNA（siRNA）抑制IL-8表达导致正常尿路上皮细胞死亡。加入重组人IL-8拯救了用IL-8 siRNA处理的正常尿路上皮细胞。这种拯救作用可以被IL-8受体CXCR 1的抗体阻断，但不能被CXCR 2阻断，这表明正常尿路上皮细胞通常具有IL-8自分泌或旁分泌活性，用于CXCR 1介导的存活和生长。间质性膀胱炎患者的样本中IL-8 mRNA水平较低，间质性膀胱炎是一种与尿路上皮细胞功能障碍和/或丧失相关的膀胱疾病。总之，这些结果表明，IL-8是一个重要的正常尿路上皮生长因子，是必要的正常尿路上皮细胞在体外和体内的生存。膀胱中较低的IL-8表达水平可能有助于间质性膀胱炎的病理生理学。
Tseng-Rogenski S, Liebert M. Interleukin-8 is essential for normal urothelial cell survival. Am J Physiol Renal Physiol 297: F816-F821, 2009. First published June 17, 2009; doi:10.1152/ajprenal.90733.2008.-Interleukin-8 (IL-8; CXCL8) has been shown to play a role in multiple cellular processes. Here, we report an additional role of IL-8 as a growth and essential survival factor for normal human urothelial cells. Supplementing exogenous recombinant human IL-8 to normal urothelial cells promoted cell growth through the Akt pathway. Inhibition of IL-8 expression by small inhibitory RNA (siRNA) caused normal urothelial cells to die. Addition of recombinant human IL-8 rescued the normal urothelial cells treated with IL-8 siRNA. This rescue effect could be blocked by antibodies to the IL-8 receptor CXCR1 but not by CXCR2, suggesting that normal urothelial cells normally have IL-8 autocrine or paracrine activity for survival and growth mediated by CXCR1. IL-8 mRNA levels were lower in samples from patients with interstitial cystitis, a urinary bladder disorder associated with urothelial cell dysfunction and/or loss. Taken together, these results suggest that IL-8 is an important normal urothelial growth factor and is necessary for normal urothelial cell survival in vitro and in vivo. Lower IL-8 expression levels in the urinary bladder may contribute to pathophysiology of interstitial cystitis.