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 Jun;37(4):179-86. doi: 10.1016/s1056-8719(97)00016-6.


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.

Publication types

  • Comparative Study

MeSH terms

  • 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


  • Anti-Inflammatory Agents, Non-Steroidal
  • Cyclooxygenase 2 Inhibitors
  • Cyclooxygenase Inhibitors
  • Isoenzymes
  • Lipopolysaccharides
  • Membrane Proteins
  • Arachidonic Acid
  • Thromboxane B2
  • Cyclooxygenase 1
  • Cyclooxygenase 2
  • PTGS1 protein, human
  • PTGS2 protein, human
  • Prostaglandin-Endoperoxide Synthases