Protein holds hope for arthritis, say researchers

Scientific serendipity leads UBC scientists to discovery that may result in new treatments for inflammation

A protein that reduces inflammation has been discovered by a group of UBC researchers.

The finding, reported in Science last month, may pave the way for new treatments of chronic inflammatory diseases such as arthritis, gingivitis, and lung disease.

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

"These results are an example of scientific serendipity," says Dr. Robert Phillips, executive director of the National Cancer Institute of Canada, which supported Overall's research with funds from the Canadian Cancer Society.

"This discovery holds exciting possibilities for treating chronic inflammatory diseases."

"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," says 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."

In chronic diseases such as gingivitis or arthritis something goes wrong with the signals, Overall says, 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," he says. "But we had a bigger surprise that not only was the green light removed, but the red light came on. Now the movement of these cells was stopped."

Tests revealed that there is a 40 per cent reduction in inflammation when the new form of MCP-3 is administered.

Prof. Ian Clark-Lewis at UBC's Biomedical Research Centre synthesized the new form of MCP-3 for testing by Prof. Chris McCulloch 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 that understanding these very complicated processes may lead to new drug discoveries," says Overall.

reading list

Science magazine (Aug. 18 issue)

Research programs in Dentistry

Vancouver Sun article (excerpt)

National Cancer Institute of Canada