UC Davis researchers discover new drug target for inflammato...( (SACRAMENTO Calif.) UC Davis resear...)

(SACRAMENTO, Calif.) UC Davis researchers have defined a cellular process that promotes inflammation and, at the same time, found an important starting point for identifying and testing new drugs for diseases such as sepsis, rheumatoid arthritis, cardiovascular disease and some cancers.

The scientists discovered that a protein called sPLA2-IIA binds to two integrins labeled alpha-V-beta-3 and alpha-4-beta-1, causing them to rapidly multiply and boosting an immune system response already gone awry due to disease.

"We have known for a while that this protein is elevated with inflammation," said Yoshikazu Takada, UC Davis professor of dermatology and lead author of the study, which appears in the September 19 issue of The Journal of Biological Chemistry. "Our outcome shows with much more precision how the protein actually works to advance inflammation. The potential impact of the finding on our ability to block inflammation and stop the disease process in its tracks is enormous."

Protein sPLA2-IIA has been a major drug discovery target for years, but efforts to counteract the protein have yielded mixed results. Takada explains that this is due to the fact that its intercellular relationships in humans were not well-known. Scientists have previously identified receptors for the protein in mice cells. However, Takada and his team are the first to find that the protein binds to completely different receptors the two integrins in human cells.

Integrins are the "networkers" of the immune system, playing key roles in the attachment of cells to other cells. Integrins are also important to signal transduction, the process by which a cell transforms from one kind of signal or stimulus into another.

"We need to know the mechanisms of inflammation to be able to disrupt it," said Takada. "Now that we know more about how this protein interacts with these integrins, researchers can be much more successful in screening
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