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UBC researchers find key to reducing inflammation

August 16, 2000

A protein that reduces inflammation has been discovered by a group of UBC researchers. The finding, to be reported Friday in the journal Science, may pave the way for new treatments of chronic inflammatory diseases such as arthritis, gingivitis, and lung disease.

The Canadian research team led by Prof. Chris Overall at UBC's Faculty of Dentistry, discovered how one of the natural signals -- MCP-3 -- the human body uses to turn off inflammation while studying how cancer cells spread.

"MCP-3 is like a traffic signal with a green and red light that tells the macrophages -- white blood cells that rid the body of damaged tissue -- when and where to go," said Overall.

"Like any accident, it is important to get help, but when everything is fixed, the body then needs to be told to stop sending more 'ambulances' to the problem spot, or else things clog up and break down again."

Overall explains that in chronic diseases like gingivitis or arthritis something goes wrong with the signals and the flow of white blood cells continues, leading to chronic inflammation and long-term tissue damage.

Angus McQuibban, a UBC biochemistry doctoral student working in Overall's lab, discovered a new form of MCP-3 that halts the flow of the white blood cells. He found that an enzyme called gelatinase made during inflammation trimmed the end of MCP-3 molecules and led to the new form of the protein.

McQuibban likens it to shooting out the green light on a traffic signal. "There is now no more signal. But we had a bigger surprise to find that not only was the 'green light' removed, but that the 'red light' then came on. Now the movement of these cells was stopped."

Tests revealed that there was a 40 per cent reduction in inflammation when the new form of MCP-3 was administered. Prof. Ian Clark-Lewis at UBC's Biomedical Research Centre synthesized the new form of MCP-3 for testing by Prof. Chris McCullouch at the University of Toronto's Faculty of Dentistry.

"What we are trying to do now is to work out how these signals go wrong in diseases like cancer, arthritis and periodontitis with the hope we can understand in molecular detail these very complicated processes that may lead to new drug discoveries," said Overall.

In the meantime, the new form of MCP-3 has been patented at UBC and is being evaluated as a new anti-inflammatory drug.
-end-
The team's research is being funded by a grant from the National Cancer Institute of Canada and the Canadian Cancer Society.

University of Toronto

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