Blockade of interleukin-8 receptor signalling inhibits cyst development in vitro, via suppression of cell proliferation in autosomal polycystic kidney disease.
OBJECTIVE
Autosomal dominant polycystic kidney disease (ADPKD) is a highly prevalent inherited disorder and results in the progressive development of cysts in both kidneys. In recent studies, several cytokines and growth factors secreted by the cyst-lining epithelia were identified to be upregulated and promote cyst growth. According to our previous study, chemokines with a similar amino acid sequence as human interleukin-8 (IL-8) are highly expressed in a rodent model with renal cysts. Therefore, in this study, we focused on whether IL-8 signalling is associated with renal cyst formation, and tested the possibility of IL-8 as a new therapeutic target for ADPKD.


METHODS
Expression of IL-8 and its receptor were screened either by enzyme linked immunosorbent assay (ELISA) or Western blot. Inhibited IL-8 signalling by antagonist for IL-8 receptor or gene silencing was tested in molecular levels, mainly through Western blot. And cell proliferation was measured by XTT assays. Finally, a three-dimensional culture was performed to understand how IL-8 affected cyst formation, in vitro.


RESULTS
Interleukin-8 secretion and expression of its receptor highly increased in two different human ADPKD cell lines (WT9-7 and WT9-12), compared to normal human renal cortical epithelial cell line. Cell proliferation, which is mediated by IL-8 signal, was inhibited either by an antagonist or siRNA targeting for IL-8 receptor. Finally, a three-dimensional culture showed an alleviation of cystogenesis in vitro, after blocking the IL-8 receptor signals.


CONCLUSIONS
These results suggest that IL-8 and its signalling molecules could be new biomarkers and a therapeutic target of ADPKD.
Department of Biological Science, Sookmyung Women's University, Seoul, Korea.
Eun Ji
EJ
Lee
Seon Ah
SA
Song
Hyo Won
HW
Mun
Kyung Hyun
KH
Yoo
Soo Young
SY
Choi
Eun Young
EY
Park
Jong Hoon
JH
Park
D049109:Cell Proliferation / Q000187:drug effects*; D002478:Cells, Cultured; D006801:Humans; D016209:Interleukin-8 / Q000502:physiology*; D016891:Polycystic Kidney, Autosomal Dominant / Q000188:drug therapy* / Q000209:etiology* / Q000473:pathology; D053700:Receptors, Interleukin-8 / Q000037:antagonists & inhibitors*; D015398:Signal Transduction / Q000187:drug effects*
D016209:Interleukin-8; D053700:Receptors, Interleukin-8
Autosomal polycystic kidney disease; cystogenesis; interleukin-8