Interleukin-19 as a translational indicator of renal injury.
Accurate detection and prediction of renal injury are central not only to improving renal disease management but also for the development of new strategies to assess drug safety in pre-clinical and clinical testing. In this study, we utilised the well-characterised and differentiated human renal proximal tubule cell line, RPTEC/TERT1 in an attempt to identify markers of renal injury, independent of the mechanism of toxicity. We chose zoledronate as a representative nephrotoxic agent to examine global transcriptomic alterations using a daily repeat bolus protocol over 14 days, reflective of sub-acute or chronic injury. We identified alterations in targets of the cholesterol and mevalonate biosynthetic pathways reflective of zoledronate specific effects. We also identified interleukin-19 (IL-19) among other inflammatory signals such as SERPINA3 and DEFB4 utilising microarray analysis. Release of IL-19 protein was highly induced by an additional four nephrotoxic agents, at magnitudes greater than the characterised marker of renal injury, lipocalin-2. We also demonstrate a large increase in levels of IL-19 in urine of patients with chronic kidney disease, which significantly correlated with estimated glomerular filtration rate levels. We suggest IL-19 as a potential new translational marker of renal injury.
Division of Physiology, Department of Physiology and Medical Physics, Innsbruck Medical University, 6020, Innsbruck, Austria.
Paul
P
Jennings
Daniel
D
Crean
Lydia
L
Aschauer
Alice
A
Limonciel
Konrad
K
Moenks
Georg
G
Kern
Philip
P
Hewitt
Karl
K
Lhotta
Arno
A
Lukas
Anja
A
Wilmes
Martin O
MO
Leonard
D015415:Biomarkers / Q000032:analysis / Q000652:urine; D018929:Cell Culture Techniques; D002460:Cell Line; D004164:Diphosphonates / Q000633:toxicity; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D007093:Imidazoles / Q000633:toxicity; D007378:Interleukins / Q000096:biosynthesis* / Q000235:genetics / Q000652:urine; D007687:Kidney Tubules, Proximal / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D051436:Renal Insufficiency, Chronic / Q000139:chemically induced* / Q000235:genetics / Q000652:urine; D000077211:Zoledronic Acid
D015415:Biomarkers; D004164:Diphosphonates; C421250:IL19 protein, human; D007093:Imidazoles; D007378:Interleukins; D000077211:Zoledronic Acid