Journal
AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY
Volume 297, Issue 3, Pages F816-F821Publisher
AMER PHYSIOLOGICAL SOC
DOI: 10.1152/ajprenal.90733.2008
Keywords
growth factor; interstitial cystitis; CXCR1; CXCL8
Categories
Funding
- National Institute of Diabetes and Digestive
- Kidney Diseases National Institutes of Health [R21-DK-66077]
- NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES [R21DK066077] Funding Source: NIH RePORTER
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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.
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