Podocytes Express IL-6 and Lipocalin 2/ Neutrophil Gelatinase-Associated Lipocalin in Lipopolysaccharide-Induced Acute Glomerular Injury

Abstract

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.

RETRACTION: Angiotensin II and Canonical Transient Receptor Potential-6 Activation Stimulate Release of a Signal Transducer and Activator of Transcription 3–Activating Factor from Mouse Podocytes

“…The role of gp130 signaling in podocytes is not well understood and has only been studied in the role of IL-6 signaling in this cell type (Kim and Park, 2013). In rat podocytes, IL-6 evokes an increase in expression of apoptotic markers that coincides with stimulation of p53 expression (Kim and Park, 2013), along with expression of inflammatory markers (Lee et al, 2012). …”

Urinary biomarkers for podocyte injury: Significance for evaluating the course and prognosis of chronic glomerulonephritis

“…Клетки ме-зангия, а также макрофаги, лимфоциты и эндотелиальные клетки могут секретировать ИЛ-6 в ответ на воздействие факторов воспаления [13]. Однако в биоптатах почек па-циентов со значительной мочевой экскрецией ИЛ-6 не находят мононуклеарных и лимфоцитарных инфильтра-тов, что предполагает наличие и другого источника этого фактора [14]. Полагают, что таким источником ИЛ-6 мо-гут быть ПД.…”

Tribbles Homolog 3 Attenuates Mammalian Target of Rapamycin Complex-2 Signaling and Inflammation in the Diabetic Kidney

“…11 To localize the site of Lcn2/Ngal production, we performed in situ RNA hybridization and observed glomerular expression of Lcn2/ Ngal in the diabetic WT and TRB3 2/2 mice (Supplemental Figure 2). , and studies have shown that in certain cell types TRB3 inhibits the phosphorylation of AKT.…”

“…11,76 Primary podocytes were propagated from kidneys from 6-to 10-week-old WT and TRB3 2/2 mice with Dynabeads (Life Technologies, Grand Island, NY) as we have previously reported. Passage 2 cells were used, and for validation they were grown on cover slips and stained with antisynaptopodin antibody (clone G1D4; Fitzgerald Industries, Acton, MA).…”