Anemia upregulates lipocalin 2 in the liver and serum

Abstract

Lipocalin 2 (Lcn2), a mammalian protein that is expressed and secreted in various pathologic states, binds siderophores, which are high-affnity iron chelators. Besides its role in limiting iron availability to pathogens in the setting of bacterial infection, Lcn2:siderophore complexes can also deliver iron to cells. In this study, we examined Lcn2 regulation in the liver of mice in situations of increased iron utilization, namely, during anemia. Anemia induced by phlebotomy, iron deprivation, or phenylhydrazine treatment was associated with upregulation of Lcn2 gene expression in the liver and elevation of serum Lcn2 protein levels. We further explored the participation of several factors known to co-occur during anemia, including hypoxia, changes in iron levels, and erythropoietic drive, in the regulation of Lcn2 by anemia. We found that hypoxia, but not iron or erythropoietin, caused an induction of Lcn2 expression. The upregulation of Lcn2 levels by anemia and hypoxia, which is not directly mediated by iron or erythropoietin, suggests a possible physiological role for Lcn2 during increased iron utilization and mobilization from stores.

C-reactive protein but not hepcidin, NGAL and transferrin determines the ESA resistance in hemodialysis patients

“…Anemia and inflammation are known to induce NGAL. 33,34 In this study, we could not demonstrate any association between serum NGAL levels and CRP. Serum NGAL levels were higher in HD patients compared with healthy controls in our study confirming the previous studies 33 probably due to decreased clearance rather than increased inflammation in HD patients.…”

Neutrophil Gelatinase-Associated Lipocalin induces the expression of heme oxygenase-1 and superoxide dismutase 1, 2

“…It has been reported that hypoxic stress and acute infraction increase Lcn2 expression in mouse macrophages (Hemdahl et al 2006, Jiang et al 2008). This supports the idea that expression of lipocalin-2 is a response that these cells show against hypoxic stress.…”

Bacterial Cell Wall Constituents Induce Hepcidin Expression in Macrophages Through MyD88 Signaling

“…Hepcidin (Hamp) and β-actin mRNA levels were measured by real-time PCR in a Rotor Gene 3000™ Real-Time DNA Detection System (Montreal Biotech, Inc., Kirkland, QC, Canada) with the QuantiTect SYBR Green I PCR kit (Qiagen, Mississauga, ON, Canada), as described [20,21], and expression levels of hepcidin and IL-6 were normalized to the housekeeping gene β-actin. The primers employed were: β-actin-5′-…”