Interleukin-8 is essential for normal urothelial cell survival.
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.
Tseng-Rogenski
Stephanie
S
Department of Urology, University of Michigan, Ann Arbor, Michigan 48109, USA.
Liebert
Monica
M
D049109:Cell Proliferation; D002470:Cell Survival; D002478:Cells, Cultured; D018856:Cystitis, Interstitial / Q000276:immunology* / Q000473:pathology; D006801:Humans; D016209:Interleukin-8 / Q000235:genetics / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D034622:RNA Interference; D012333:RNA, Messenger / Q000378:metabolism; D023062:Receptors, Interleukin-8A / Q000378:metabolism; D011994:Recombinant Proteins / Q000378:metabolism; D015398:Signal Transduction; D013997:Time Factors; D014513:Ureter / Q000276:immunology* / Q000473:pathology; D001743:Urinary Bladder / Q000276:immunology* / Q000473:pathology; D019459:Urothelium / Q000276:immunology / Q000473:pathology
C508606:CXCL8 protein, human; D016209:Interleukin-8; D012333:RNA, Messenger; D023062:Receptors, Interleukin-8A; D011994:Recombinant Proteins; D051057:Proto-Oncogene Proteins c-akt