Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
SHR Neuro Krebs Kardio Lipid Stoffw Microb
Eller, K; Schroll, A; Banas, M; Kirsch, AH; Huber, JM; Nairz, M; Skvortsov, S; Weiss, G; Rosenkranz, AR; Theurl, I.
Lipocalin-2 expressed in innate immune cells is an endogenous inhibitor of inflammation in murine nephrotoxic serum nephritis.
PLoS One. 2013; 8(7):e67693-e67693
Doi: 10.1371/journal.pone.0067693
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- Führende Autor*innen der Med Uni Graz
- Eller Kathrin
- Co-Autor*innen der Med Uni Graz
- Kirsch Alexander
- Rosenkranz Alexander
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- Abstract:
- Lipocalin-2 (Lcn-2) is involved in divergent processes such as acute kidney injury or bacterial host defence. Our study was designed to evaluate the functional role of Lcn-2 in nephrotoxic serum nephritis (NTS). Since Lcn-2 is expressed in tubular epithelial cells as well as in cells of innate immunity such as macrophages and polymorphonuclear neutrophils (PMN), we induced NTS in wild-type (WT), Lcn-2 knock-out (KO) mice and WT/Lcn-2 KO chimeras. Mice lacking Lcn-2 exhibited more glomerular damage with increased proteinuria and interstitial leukocyte accumulation compared to WT mice. Chimeras able to express Lcn-2 in macrophages and PMN but not in epithelial cells were found to develop NTS comparable to wild-type controls. In contrast, chimeras expressing Lcn-2 in tubular epithelial cells with no expression in innate immune cells developed increased NTS due to decreased concerted apoptosis but increased necrosis and formation of damage-associated molecular patterns (DAMPs) such as high-mobility group box 1 (HMGB-1) in the kidney. In vivo blockade of HMGB-1, a toll-like receptor (TLR)-2 agonist, significantly reduced inflammation and NTS in Lcn-2 knock-out mice. In parallel, TLR-2 signalling was found to drive Lcn-2 transcription in vitro. Taken together, Lcn-2 expressed in innate immune cells is protective in NTS by inducing concerted apoptosis and inhibiting the formation of HMGB-1 thereby limiting cytokine production via TLR-2 signalling. In parallel, TLR-2 dependent transcription of Lcn-2 is an endogenous inhibitor of inflammation in NTS.
- Find related publications in this database (using NLM MeSH Indexing)
- Acute-Phase Proteins - deficiency
- Animals -
- Apoptosis -
- Cytokines - biosynthesis
- Female -
- Gene Expression Regulation -
- HMGB1 Protein - genetics
- Immunity, Innate -
- Inflammation -
- Kidney Glomerulus - immunology
- Lipocalins - genetics
- Macrophages - immunology
- Mice -
- Mice, Knockout -
- Nephritis - genetics
- Neutrophils - immunology
- Oncogene Proteins - deficiency
- Proteinuria - genetics
- RNA, Small Interfering - genetics
- Signal Transduction -
- Toll-Like Receptor 2 - antagonists & inhibitors