Podocytes express IL-6 and lipocalin 2/ neutrophil gelatinase-associated lipocalin in lipopolysaccharide-induced acute glomerular injury.
Bottom Line: Plasma levels of interleukin (IL)-6 predict the development of AKI and are associated with higher mortality in ICU patients with AKI.Surprisingly, in direct response to exogenous IL-6, podocytes produce lipocalin-2/neutrophil gelatinase-associated lipocalin (Lcn2/Ngal).The glomerulus is involved in septic AKI, and we demonstrate that podocytes secrete key mediators of AKI including IL-6 and Lcn2/Ngal.
Affiliation: Research Service and Division of Nephrology-Hypertension, Veterans Affairs San Diego Healthcare System, Veterans Medical Research Foundation, San Diego, CA 92161, USA.Show MeSH
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Mentions: To investigate whether LPS had similar effects on podocyte secretion of Lcn2/Ngal, we treated fully differentiated podocytes with LPS. LPS rapidly and potently stimulated Lcn2/Ngal mRNA production in podocytes to levels nearly 20-fold greater than treatment with exogenous IL-6 (fig. 4a). In contrast to the burst of IL-6 mRNA expression (which was dramatically reduced by 4 h) observed after LPS exposure, Lcn2/Ngal mRNA expression increased with LPS treatment in a time-dependent manner. By 24 h, there was a 1,100-fold increase in Lcn2/Ngal mRNA expression with supernatant concentrations of Lcn2/Ngal of 29,370 pg/ml. Western blotting performed on culture supernatants confirmed these findings (fig. 4c).
Affiliation: Research Service and Division of Nephrology-Hypertension, Veterans Affairs San Diego Healthcare System, Veterans Medical Research Foundation, San Diego, CA 92161, USA.