Eller, Kathrin and Schroll, Andrea and Banas, Miriam and Kirsch, Alexander H. and Huber, Julia M. and Nairz, Manfred and Skvortsov, Sergej and Weiss, Guenter and Rosenkranz, Alexander R. and Theurl, Igor (2013) Lipocalin-2 Expressed in Innate Immune Cells Is an Endogenous Inhibitor of Inflammation in Murine Nephrotoxic Serum Nephritis. PLOS ONE, 8 (7): e67693. ISSN 1932-6203,
Full text not available from this repository. (Request a copy)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.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | GELATINASE-ASSOCIATED LIPOCALIN; REGULATORY T-CELLS; BASEMENT-MEMBRANE GLOMERULONEPHRITIS; ISCHEMIA-REPERFUSION INJURY; HUMAN NEUTROPHIL GELATINASE; RENAL INJURY; KIDNEY INJURY; MAST-CELLS; NGAL; IRON; |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Innere Medizin II |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 06 Apr 2020 09:41 |
| Last Modified: | 06 Apr 2020 09:41 |
| URI: | https://pred.uni-regensburg.de/id/eprint/16377 |
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