Podocytes express IL-6 and lipocalin 2/neutrophil gelatinase-associated lipocalin in lipopolysaccharide-induced acute glomerular injury

SJ Lee, E Borsting, AE Declèves, P Singh… - Nephron Experimental …, 2013 - karger.com
SJ Lee, E Borsting, AE Declèves, P Singh, R Cunard
Nephron Experimental Nephrology, 2013karger.com
Background/Aims: Acute kidney injury (AKI) contributes to significant morbidity and mortality
in the intensive care unit (ICU). Plasma levels of interleukin (IL)-6 predict the development of
AKI and are associated with higher mortality in ICU patients with AKI. Most studies in AKI
have focused on the tubulo-interstitium, despite evidence of glomerular involvement. In the
following study, our goals were to investigate the expression of IL-6 and its downstream
mediators in septic-induced AKI. Methods: Podocytes were treated in vitro with …
Background/Aims
Acute kidney injury (AKI) contributes to significant morbidity and mortality in the intensive care unit (ICU). Plasma levels of interleukin (IL)-6 predict the development of AKI and are associated with higher mortality in ICU patients with AKI. Most studies in AKI have focused on the tubulo-interstitium, despite evidence of glomerular involvement. In the following study, our goals were to investigate the expression of IL-6 and its downstream mediators in septic-induced AKI.
Methods
Podocytes were treated in vitro with lipopolysaccharide (LPS) and mice were treated with LPS, and we evaluated IL-6 expression by real-time PCR, ELISA and in situ RNA hybridization.
Results
Following LPS stimulation, IL-6 is rapidly and highly induced in cultured podocytes and in vivo in glomeruli and infiltrating leukocytes. Surprisingly, in direct response to exogenous IL-6, podocytes produce lipocalin-2/neutrophil gelatinase-associated lipocalin (Lcn2/Ngal). LPS also potently induces Lcn2/Ngal expression in podocytes in culture and in glomeruli in vivo. Intense Lcn2/Ngal expression is also observed in IL-6 knockout mice, suggesting that while IL-6 may be sufficient to induce glomerular Lcn2/Ngal expression, it is not essential.
Conclusions
The glomerulus is involved in septic AKI, and we demonstrate that podocytes secrete key mediators of AKI including IL-6 and Lcn2/Ngal.
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