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Am J Physiol Renal Physiol 297: F816-F821, 2009. First published June 17, 2009; doi:10.1152/ajprenal.90733.2008
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Interleukin-8 is essential for normal urothelial cell survival

Stephanie Tseng-Rogenski and Monica Liebert

Department of Urology, University of Michigan, Ann Arbor, Michigan

Submitted 5 December 2008 ; accepted in final form 11 June 2009

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.

growth factor; interstitial cystitis; CXCR1; CXCL8


Address for reprint requests and other correspondence: M. Liebert, Univ. of Michigan, 3875 Taubman Center PCS 5330, 1500 E. Medical Center Drive, Ann Arbor, MI 48109-5330 (e-mail: monical{at}umich.edu)






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