Stimulation of Mesangial Cells by Angiotensin II and Lipopolysaccharide Increases Expression of lnterleukin-18, but Not IL-18 Receptor

摘要

Background/Aims: Mesangial cell (MC) hyperplasia is associated with several kidney diseases. Experimental studies confirm upregulation of IL-18 in glomerulardisease and renal allograft rejection. We evaluated whether MCs express IL-18 and IL-18 receptor-a (IL-18Ralpha) with and without stimulation by LPS, Angll and PDGF. Methods: Glomeruli were isolated using Dynabeads perfusion. MCs were cultured by glomeru-lar explantation. IL-18 and IL-18Ralpha expression were detected by RT-PCR, ELISA and flow cytometry. Results: Significantly higher levels of IL-18 expression were detected in isolated glomeruli, compared to cortical tissue devoid of glomeruli, and in MCs, compared to tubular cells (both p < 0.01). Increased IL-18 expression was detected in MCs, but not podo-cytes, endothelial cells or tubular cells in response to LPS stimulation. IL-18 mRNA and protein expression were significantly upregulated by Angll (p < 0.05) and LPS (p < 0.01), but not PDGF-BB, in primary MCs and a MC line (MES13). IL-18Ralpha mRNA was almost undetectable in MCs treated with or without LPS, Angll and PDGF-BB. IL-18Ralpha protein was not detect-ed by flow cytometry. Conclusions: MCs express IL-18, which was significantly increased after LPS and Angll stimulation, but do not express appreciable levels of IL-18Ralpha. MC-derived IL-18 is unlikely to be an autocrine mediator in glomerular disease given the lack of IL-18Ralpha.