Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
SHR Neuro Krebs Kardio Lipid Stoffw Microb
Yang, M; Ramachandran, A; Yan, HM; Woolbright, BL; Copple, BL; Fickert, P; Trauner, M; Jaeschke, H.
Osteopontin is an initial mediator of inflammation and liver injury during obstructive cholestasis after bile duct ligation in mice.
Toxicol Lett. 2014; 224(2):186-195
Doi: 10.1016/j.toxlet.2013.10.030
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- Co-Autor*innen der Med Uni Graz
- Fickert Peter
- Trauner Michael
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- Abstract:
- Osteopontin (OPN) is a chemotactic factor which can be cleaved to the pro-inflammatory form by matrix metalloproteinases (MMPs). To test the hypothesis that OPN can modulate inflammatory liver injury during cholestasis, wild-type (WT) C57BL/6 and OPN knockout (OPN-KO) mice underwent bile duct ligation (BDL). OPN-KO mice showed significant reduction in liver injury (plasma ALT and necrosis) and neutrophil recruitment compared with WT animals at 24h but not 72h after BDL. In WT mice, a 4-fold increase in hepatic MMP-3 mRNA and elevated MMP activities and cleaved OPN levels were observed in bile. WT mice subjected to BDL in the presence of the MMP inhibitor BB-94 showed reduced liver injury, less neutrophil extravasation and diminished levels of cleaved OPN in bile. Thus, during obstructive cholestasis, OPN released from biliary epithelial cells could be cleaved by MMPs in bile. When the biliary system leaks, cleaved OPN enters the parenchyma and attracts neutrophils. In the absence of OPN, other chemoattractants, e.g. chemokines, mediate a delayed inflammatory response and injury. Taken together, our data suggest that OPN is the pro-inflammatory mediator that initiates the early neutrophil-mediated injury phase during obstructive cholestasis in mice. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.
- Find related publications in this database (using NLM MeSH Indexing)
- Alanine Transaminase - blood
- Animals -
- Bile Acids and Salts - toxicity
- Bile Ducts - surgery
- Cholestasis - complications
- Inflammation - etiology
- Ligation -
- Male -
- Matrix Metalloproteinase 3 - genetics
- Mice -
- Mice, Inbred C57BL -
- Neutrophil Infiltration -
- Osteopontin - genetics Osteopontin - physiology
- Phenylalanine - analogs & derivatives Phenylalanine - pharmacology
- Thiophenes - pharmacology
- Find related publications in this database (Keywords)
- Inflammatory liver injury
- Cholestasis
- Bile duct ligation
- Osteopontin
- Neutrophils