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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
biochemistry, genetics and molecular biology
Ethyl pyruvate and ethyl lactate down-regulate the production of pro-inflammatory cytokines and modulate expression of immune receptors
Biochemical Pharmacology, Volume 76, No. 5, Year 2008
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Description
Esters of α-oxo-carbonic acids such as ethyl pyruvate (EP) have been demonstrated to exert inhibitory effects on the production of anti-inflammatory cytokines. So far, there is no information about effects, if any, of ethyl lactate (EL), an obviously inactive analogue of EP, on inflammatory immune responses. In the present study, we provide evidence that the anti-inflammatory action of α-oxo-carbonic acid esters is mediated by inhibition of glyoxalases (Glo), cytosolic enzymes that catalyse the conversion of α-oxo-aldehydes such as methylglyoxal (MGO) into the corresponding α-hydroxy acids using glutathione as a cofactor. In vitro enzyme activity measurements revealed the inhibition of human Glo1 by α-oxo-carbonic acid esters, whilst α-hydroxy-carbonic acid esters such as EL were not inhibitory. In contrast, both EP and EL were shown to suppress the Lipopolysaccharide (LPS)-induced production of pro-inflammatory cytokines such as tumor necrosis factor-α, interleukin (IL)-1β, IL-6 and IL-8 from human immunocompetent cells, and modulated the expression of the immune receptors HLA-DR, CD14 and CD91 on human monocytes. Here, we show a crossing link between glyoxalases and the immune system. The results described herein introduce glyoxalases as a possible target for therapeutic approaches of immune suppression. © 2008 Elsevier Inc. All rights reserved.
Authors & Co-Authors
Hollenbach, Marcus
Germany, Leipzig
Universität Leipzig
Hintersdorf, Anja
Germany, Leipzig
Universität Leipzig
Huse, Klaus
Germany, Jena
Leibniz Institute on Aging - Fritz Lipmann Institute
Sack, Ulrich
Germany, Leipzig
Institute of Clinical Immunology and Transfusion Medicine
Germany, Leipzig
Fraunhofer Institute for Cell Therapy and Immunology Izi
Bigl, Marina
Germany, Leipzig
Universität Leipzig
Groth, Marco
Germany, Leipzig
Universität Leipzig
Germany, Jena
Leibniz Institute on Aging - Fritz Lipmann Institute
Santel, Thore
Germany, Leipzig
Universität Leipzig
Buchold, Martin
Germany, Leipzig
Universität Leipzig
Lindner, Inge
Germany, Leipzig
Universität Leipzig
Otto, Andreas
Germany, Leipzig
Universität Leipzig
Sicker, Dieter
Germany, Leipzig
Institute of Analytical Chemistry
Schellenberger, Wolfgang
Germany, Leipzig
Universität Leipzig
Almendinger, Johannes
Germany, Leipzig
Institute of Virology
Pustowoit, Barbara
Germany, Leipzig
Institute of Virology
Birkemeyer, Claudia S.
Germany, Leipzig
Institute of Physiological Chemistry
Platzer, Matthias
Germany, Jena
Leibniz Institute on Aging - Fritz Lipmann Institute
Oerlecke, Ilka
Germany, Leipzig
Universität Leipzig
Hemdan, Nasr Y.A.
Germany, Leipzig
Institute of Clinical Immunology and Transfusion Medicine
Germany, Leipzig
Fraunhofer Institute for Cell Therapy and Immunology Izi
Egypt, Alexandria
Faculty of Science
Birkenmeier, Gerd
Germany, Leipzig
Universität Leipzig
Statistics
Citations: 42
Authors: 19
Affiliations: 8
Identifiers
Doi:
10.1016/j.bcp.2008.06.006
ISSN:
00062952
Research Areas
Cancer