Knock-In Mice Expressing a 15-Lipoxygenating Alox5 Mutant Respond Differently to Experimental Inflammation Than Reported Alox5−/− Mice

Metabolites

Laura Kutzner¹  Nils Helge Schebb¹  Pallu Reddanna²  Dagmar Heydeck³  Hartmut Kuhn³  Eugenia Marbach-Breitrück³  Dominika Labuz⁴  Halina Machelska⁴  Karsten H. Weylandt⁵  Nadine Rohwer⁵  Silvina Romero-Suarez⁶  Carmen Infante-Duarte⁶  Michael Rothe⁷  Lothar H. Wieler⁸ 

[1] Chair of Food Chemistry, Faculty of Mathematics and Natural Sciences, University of Wuppertal, Gaussstraße 20, 42119 Wuppertal, Germany;Department of Animal Biology, School of Life Sciences, University of Hyderabad, Gachibowli, Hyderabad 500046, Andhra Pradesh, India;Department of Biochemistry, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Chariteplatz 1, 10117 Berlin, Germany;Department of Experimental Anesthesiology, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Hindenburgdamm 30, 12203 Berlin, Germany;Division of Medicine, Department of Gastroenterology, Metabolism and Oncology, Ruppin General Hospital, Brandenburg Medical School, Fehrbelliner Straße 38, 16816 Neuruppin, Germany;Institute for Medical Immunology, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Augustenburger Platz 1, 13353 Berlin, Germany;Lipidomix GmbH, Robert-Rössle-Straße 10, 13125 Berlin, Germany;Robert Koch Institute, Nordufer 20, 13353 Berlin, Germany;

关键词: eicosanoids;    lipoxygenase;    inflammation;    pain;    leukotrienes;    resolvins;   

DOI  :  10.3390/metabo11100698

来源: DOAJ

【 摘 要 】

Arachidonic acid 5-lipoxygenase (ALOX5) is the key enzyme in the biosynthesis of pro-inflammatory leukotrienes. We recently created knock-in mice (Alox5-KI) which express an arachidonic acid 15-lipoxygenating Alox5 mutant instead of the 5-lipoxygenating wildtype enzyme. These mice were leukotriene deficient but exhibited an elevated linoleic acid oxygenase activity. Here we characterized the polyenoic fatty acid metabolism of these mice in more detail and tested the animals in three different experimental inflammation models. In experimental autoimmune encephalomyelitis (EAE), Alox5-KI mice displayed an earlier disease onset and a significantly higher cumulative incidence rate than wildtype controls but the clinical score kinetics were not significantly different. In dextran sodium sulfate-induced colitis (DSS) and in the chronic constriction nerve injury model (CCI), Alox5-KI mice performed like wildtype controls with similar genetic background. These results were somewhat surprising since in previous loss-of-function studies targeting leukotriene biosynthesis (Alox5^−/− mice, inhibitor studies), more severe inflammatory symptoms were observed in the EAE model but the degree of inflammation in DSS colitis was attenuated. Taken together, our data indicate that these mutant Alox5-KI mice respond differently in two models of experimental inflammation than Alox5^−/− animals tested previously in similar experimental setups.

【 授权许可】

Unknown