In vitro effects of interleukin (IL)-1 beta inhibition on the epithelial-to-mesenchymal transition (EMT) of renal tubular and hepatic stellate cells

Journal of Translational Medicine

Maurizio Onisto¹  Amedeo Carraro²  Paola Violi²  Umberto Tedeschi²  Giovanni Gambaro³  Simona Granata⁴  Lorenzo Signorini⁴  Gloria Bellin⁴  Gianluigi Zaza⁴  Antonio Lupo⁴  Valentina Masola⁴ 

[1] Department of Biomedical Sciences, University of Padova;Department of General Surgery and Odontoiatrics, Liver Transplant Unit, University Hospital of Verona;Division of Nephrology and Dialysis, School of Medicine, Columbus-Gemelli Hospital Catholic University;Renal Unit, Department of Medicine, University-Hospital of Verona;

关键词: Epithelial to mesenchymal transition;    Canakinumab;    Fibrosis;    Liver;    Kidney;    Interleukin 1 beta;   

DOI  :  10.1186/s12967-019-1770-1

来源: DOAJ

【 摘 要 】

Abstract Background The epithelial to mesenchymal transition (EMT) is a multi-factorial biological mechanism involved in renal and hepatic fibrosis and the IL-1 beta has been assumed as a mediator of this process although data are not exhaustive. Therefore, the aim of our study was to evaluate the role of this cytokine in the EMT of renal proximal tubular epithelial cells (HK-2) and stellate cells (LX-2) and the protective/anti-fibrotic effect of its inhibition by Canakinumab (a specific human monoclonal antibody targeted against IL-1beta). Methods Both cell types were treated with IL-1 beta (10 ng/ml) for 6 and 24 h with and without Canakinumab (5 μg/ml). As control we used TGF-beta (10 ng/ml). Expression of EMT markers (vimentin, alpha-SMA, fibronectin) were evaluated through western blotting and immunofluorescence. Genes expression for matrix metalloproteinases (MMP)-2 was measured by Real-Time PCR and enzymatic activity by zymography. Cellular motility was assessed by scratch assay. Results IL-1 beta induced a significant up-regulation of EMT markers in both cell types and increased the MMP-2 protein expression and enzymatic activity, similarly to TGF-beta. Moreover, IL-1 beta induced a higher rate of motility in HK-2. Canakinumab prevented all these modifications in both cell types. Conclusions Our results clearly demonstrate the role of IL-1 beta in the EMT of renal/stellate cells and it underlines, for the first time, the therapeutic potential of its specific inhibition on the prevention/minimization of organ fibrosis.

【 授权许可】

Unknown