Stimulation of mesangial cells by angiotensin II and lipopolysaccharide increases expression of interleukin-18, but not IL-18 receptor.
OBJECTIVE
Mesangial cell (MC) hyperplasia is associated with several kidney diseases. Experimental studies confirm upregulation of IL-18 in glomerular disease and renal allograft rejection. We evaluated whether MCs express IL-18 and IL-18 receptor-α (IL-18Rα) with and without stimulation by LPS, AngII and PDGF.


METHODS
Glomeruli were isolated using Dynabeads perfusion. MCs were cultured by glomerular explantation. IL-18 and IL-18Rα 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 podocytes, endothelial cells or tubular cells in response to LPS stimulation. IL-18 mRNA and protein expression were significantly upregulated by AngII (p < 0.05) and LPS (p < 0.01), but not PDGF-BB, in primary MCs and a MC line (MES13). IL-18Rα mRNA was almost undetectable in MCs treated with or without LPS, AngII and PDGF-BB. IL-18Rα protein was not detected by flow cytometry.


CONCLUSIONS
MCs express IL-18, which was significantly increased after LPS and AngII stimulation, but do not express appreciable levels of IL-18Rα. MC-derived IL-18 is unlikely to be an autocrine mediator in glomerular disease given the lack of IL-18Rα.
Hardy
Jayne
J
Collaborative Transplantation Laboratory, Royal Prince Alfred Hospital, University of Sydney, Camperdown, N.S.W., Australia.
Hambly
Brett
B
Ko
Hongda
H
Wyburn
Kate
K
Eris
Josette
J
Yin
Jianlin
J
D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D002460:Cell Line; D006801:Humans; D020382:Interleukin-18 / Q000096:biosynthesis* / Q000172:deficiency; D008070:Lipopolysaccharides / Q000494:pharmacology*; D050527:Mesangial Cells / Q000187:drug effects* / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D053724:Receptors, Interleukin-18 / Q000096:biosynthesis*
D020382:Interleukin-18; D008070:Lipopolysaccharides; D012333:RNA, Messenger; D053724:Receptors, Interleukin-18; D000804:Angiotensin II