Zimmerman compares the signaling between blood platelets and monocytes to a pair of molecular control switches that turn Cox-2 production on and off. "It's a mechanism for precise control of Cox-2 production," he said. "But if one of the switches is turned on too high or low, it can lead to inappropriate production of Cox-2 in disease."
The first signal from the platelet tells the monocyte to turn on the gene that provides the instructions necessary to make Cox-2. These instructions are carried in small molecule called messenger RNA. When the blood platelet signals the monocyte, the cell decodes the instructions from the Cox-2 gene in a process called transcription. This results in production of messenger RNA that specifically codes for Cox-2. After the messenger RNA is transcribed, the blood platelet then sends a second signal to the monocyte that regulates stability of the Cox-2 messenger RNA and further decoding of the genetic information in a process called translation.
This results in production of the Cox-2 protein and controls how much, and at what time point, it is produced.
Drugs called non-steroidal anti-inflammatory agents, which inhibit production of Cox-2 and reduce inflammation, are some of the most widely used medications in the world for arthritis and other inflammatory diseases. But some of these drugs, also called Cox-2 inhibitors, such as Vioxx, increase the chance of heart attack.
Identifying the signaling mechanism between blood platelets and monocytes makes it possible to develop new drugs to modify Cox-2 production. "Knowing these steps gives you an initial blueprint about how to modify Cox-2," Zimmerman said. Understanding this mechanism may enable researchers to develop drugs that help people during a heart attack, or prevent heart attack, stroke or other in
Contact: Phil Sahm
University of Utah Health Sciences Center