Universität zu Köln

Busch, Daniel, Kapoor, Amar, Rademann, Pia, Hildebrand, Frank, Bahrami, Soheyl, Thiemermann, Christoph and Osuchowski, Marcin F. (2018). Delayed activation of PPAR-/ improves long-term survival in mouse sepsis: effects on organ inflammation and coagulation. Innate Immun., 24 (4). S. 262 - 274. LONDON: SAGE PUBLICATIONS LTD. ISSN 1753-4267

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Abstract

Activation of peroxisome proliferator-activated receptor (PPAR)-/ reduces tissue injury in murine endotoxemia. We hypothesized that the PPAR-/-agonist GW0742 improves long-term outcome after sepsis caused by cecal ligation and puncture (CLP). Fifty-one CD-1 female mice underwent CLP and received either vehicle (control), GW0742 (0.03mg/kg/injection; five post-CLP i.v. injections), GSK0660 (PPAR-/-antagonist) or both and were monitored for 28d. Another 20 CLP mice treated with GW0742 and vehicle were sacrificed 24h post-CLP to assess coagulopathy. Compared to vehicle, survival of CLP-mice treated with GW0742 was higher by 35% at d7 and by 50% at d28. CLP mice treated with GW0742 had 60% higher IFN- but circulating monocyte chemoattractant protein-1 and chemokine ligand were lower at 48h post-CLP. Compared to vehicle, CLP mice treated with GW0742 exhibited a 50% reduction in the circulating plasminogen activator inhibitor-1 associated with an increase in platelet number at 24h post-CLP (but no changes occurred in anti-thrombin-III, plasminogen, fibrinogen and clotting-times). CLP mice treated with GW0742 exhibited a similar increase in most of the biochemical markers of organ injury/dysfunction (lactate dehydrogenase, alanine aminotransferase, creatine kinase, creatinine, blood urea nitrogen, and triglycerides) measured. Treatment with GW0742 consistently improved long-term survival in septic CD-1 mice by partially modulating the post-CLP systemic cytokine response and coagulation systems.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Busch, Daniel UNSPECIFIED UNSPECIFIED UNSPECIFIED Kapoor, Amar UNSPECIFIED UNSPECIFIED UNSPECIFIED Rademann, Pia UNSPECIFIED UNSPECIFIED UNSPECIFIED Hildebrand, Frank UNSPECIFIED UNSPECIFIED UNSPECIFIED Bahrami, Soheyl UNSPECIFIED UNSPECIFIED UNSPECIFIED Thiemermann, Christoph UNSPECIFIED UNSPECIFIED UNSPECIFIED Osuchowski, Marcin F. UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-186964
DOI:	10.1177/1753425918771748
Journal or Publication Title:	Innate Immun.
Volume:	24
Number:	4
Page Range:	S. 262 - 274
Date:	2018
Publisher:	SAGE PUBLICATIONS LTD
Place of Publication:	LONDON
ISSN:	1753-4267
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language NF-KAPPA-B; DELTA; EXPRESSION; RECEPTORS; EPIDEMIOLOGY; BETA/DELTA; MECHANISMS; MORTALITY; RESPONSES; ALPHA Multiple languages Biochemistry & Molecular Biology; Immunology; Medicine, Research & Experimental; Microbiology Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/18696