Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
Berg, J; Christoph, T; Widerna, M; Bodenteich, A.
Isoenzyme-specific cyclooxygenase inhibitors: a whole cell assay system using the human erythroleukemic cell line HEL and the human monocytic cell line Mono Mac 6.
J Pharmacol Toxicol Methods. 1997; 37(4):179-186
Doi: 10.1016/S1056-8719(97)00016-6
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- Führende Autor*innen der Med Uni Graz
- Berg Jörg
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- Abstract:
- NSAIDs inhibit the conversion of arachidonic acid into Prostaglandin G2 and Prostaglandin H2 which is catalyzed by the enzyme cyclooxygenase (COX). Two genetically distinct isoforms have been discovered, COX-1 and COX-2. While COX-1 is thought to account for homeostatic amounts of eicosanoids, COX-2 is induced during inflammation leading to pathologic amounts of eicosanoids. Since NSAIDs inhibit both COX isoforms, antiinflammatory drug research has refocused to discovering COX-2 inhibitors that do not inhibit COX-1. For this purpose, we have developed a whole cell assay system using the human erythroleukemic cell line HEL as a source for COX-1 and the human monocytic cell line Mono Mac 6 as a source for COX-2. Mono Mac 6 cells express high amounts of COX-2 upon stimulation with lipopolysaccharide (LPS) in the absence of any detectable COX-1 protein. On the other hand, we find HEL cells to naturally express COX-1 protein, but not COX-2. Testing of a panel of NSAIDs as well as some COX-2 specific inhibitors showed that this assay system is suitable for identifying compounds that selectively inhibit either COX-1 or COX-2. This test system offers the advantage of assessing COX-1 and COX-2 inhibitors within the human species, within a similar test set-up, and circumvents the need for tedious purification of either platelets or peripheral blood monocytes.
- Find related publications in this database (using NLM MeSH Indexing)
- Anti-Inflammatory Agents, Non-Steroidal - toxicity
- Arachidonic Acid - pharmacology
- Blotting, Western -
- Cell Line -
- Cyclooxygenase 1 -
- Cyclooxygenase 2 -
- Cyclooxygenase 2 Inhibitors -
- Cyclooxygenase Inhibitors - toxicity
- Electrophoresis, Polyacrylamide Gel -
- Enzyme Induction - drug effects
- Enzyme-Linked Immunosorbent Assay -
- Humans -
- Isoenzymes - biosynthesis
- Leukemia, Erythroblastic, Acute -
- Lipopolysaccharides - pharmacology
- Membrane Proteins -
- Monocytes -
- Prostaglandin-Endoperoxide Synthases - biosynthesis
- Thromboxane B2 - analysis
- Tumor Cells, Cultured -
- Find related publications in this database (Keywords)
- NSAIDs
- prostaglandin G(2)
- cyclooxygenase inhibitors
- human erythroleukemic cell line HEL
- human monocytic cell line Mono Mac 6