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- Title
Blockade of interleukin-8 receptor signalling inhibits cyst development in vitro, via suppression of cell proliferation in autosomal polycystic kidney disease.
- Authors
Lee, Eun Ji; Song, Seon Ah; Mun, Hyo Won; Yoo, Kyung Hyun; Choi, Soo Young; Park, Eun Young; Park, Jong Hoon
- Abstract
Aim 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. Conclusion These results suggest that IL-8 and its signalling molecules could be new biomarkers and a therapeutic target of ADPKD.
- Subjects
INTERLEUKIN-8 receptors; CYSTS (Pathology); CELL proliferation; POLYCYSTIC kidney disease; CYTOKINES; EPITHELIAL cells; AMINO acid sequence
- Publication
Nephrology, 2014, Vol 19, Issue 8, p471
- ISSN
1320-5358
- Publication type
Article
- DOI
10.1111/nep.12261