Altmann, Reinhold ; Hausmann, Martin ; Spöttl, Tanja ; Gruber, Michael 
; Bull, Arthur W. ; Menzel, Katrin ; Vogl, Daniela ; Herfarth, Hans ; Schölmerich, Jürgen ; Falk, Werner ; Rogler, Gerhard
Alternative Links zum Volltext:DOIVerlag
| Dokumentenart: | Artikel |
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| Titel eines Journals oder einer Zeitschrift: | Biochemical Pharmacology |
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| Verlag: | PERGAMON-ELSEVIER SCIENCE LTD |
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| Ort der Veröffentlichung: | OXFORD |
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| Band: | 74 |
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| Nummer des Zeitschriftenheftes oder des Kapitels: | 4 |
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| Seitenbereich: | S. 612-622 |
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| Datum: | 2007 |
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| Institutionen: | Medizin > Lehrstuhl für Anästhesiologie
Medizin > Lehrstuhl für Innere Medizin I |
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| Identifikationsnummer: | | Wert | Typ |
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| 10.1016/j.bcp.2007.05.027 | DOI |
|
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| Stichwörter / Keywords: | ACTIVATED-RECEPTOR-GAMMA; INFLAMMATORY-BOWEL-DISEASE; ACID DEHYDROGENASE-ACTIVITY; MACROPHAGE GENE-EXPRESSION; NF-KAPPA-B; 13-HODE DEHYDROGENASE; LINOLEIC-ACID; ULCERATIVE-COLITIS; DIFFERENTIATION; PIOGLITAZONE; 13-oxo-ODE; endogenous ligand; 13-HODE dehydrogenase; Ulcerative colitis; PPAR gamma; colonic epithelial cells |
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| Dewey-Dezimal-Klassifikation: | 600 Technik, Medizin, angewandte Wissenschaften > 610 Medizin |
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| Status: | Veröffentlicht |
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| Begutachtet: | Ja, diese Version wurde begutachtet |
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| An der Universität Regensburg entstanden: | Ja |
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| Dokumenten-ID: | 68926 |
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Web of Science
Zusammenfassung
Background: The ligand activated nuclear hormone receptor peroxisome proliferator-activated receptor gamma (PPAR gamma) induces transcriptional repression of pro-inflammatory factors. Activation of PPAR-gamma is followed by amelioration of colitis in animal models of inflammatory bowel disease (IBD). A reduced expression of PPAR-gamma was found in epithelial cells of patients with ulcerative ...
Zusammenfassung
Background: The ligand activated nuclear hormone receptor peroxisome proliferator-activated receptor gamma (PPAR gamma) induces transcriptional repression of pro-inflammatory factors. Activation of PPAR-gamma is followed by amelioration of colitis in animal models of inflammatory bowel disease (IBD). A reduced expression of PPAR-gamma was found in epithelial cells of patients with ulcerative colitis. The eicosanoids 13-HODE and 15-HETE are products of 12/15-lipoxygenase (LOX) and endogenous ligands for PPAR gamma. Dehydrogenation of 13-HODE by 13-HODE dehydrogenase results in formation of the 13-Oxo-ODE. Highest activity of 13-HODE dehydrogenase is found in colonic epithelial cells (CECs). We therefore investigated whether 13-Oxo-ODE is a new endogenous ligand of PPAR gamma in CECs. Methods: LOX activity and 13-HODE dehydrogenase in CECs were investigated after stimulation with arachidonic or linoleic acid. LOX metabolites were identified by RP-18 reversed-phase HPLC. Binding of C-14-labelled 13-Oxo-ODE was demonstrated using a His-tagged PPAR gamma Results: Stimulation of HT-29 and primary CECs homogenates with and without Ca-ionophor was followed by the formation of high amounts of the linoleic acid metabolite 13-Oxo-ODE (155 and 8S ng/ml). The decrease of IL-8 secretion from IEC was more pronounced after pre-incubation with 13-Oxo-ODE compared to the PPAR gamma agonist troglitazone and higher as with the known PPAR gamma ligands 13-HODE and 15-HETE. Binding assays with C-14-labelled (13)Oxo-ODE clearly demonstrated a direct interaction.
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