In the current study, Takada and team evaluated the possibility of integrin binding by sPLA2-IIA using a computer program that predicts how small molecules bind to receptors. They then performed laboratory experiments using human cells to confirm the resulting predictions.
The researchers conducted additional experiments using human leukemia and lymphoma cell lines, because they are known to express integrins, in order to measure changes in the inflammatory response due to sPLA2-IIA-integrin binding. They found an increase in the number of monocytes, which are important first-line defenders for the immune system responsible for attacking foreign substances in the body. At elevated levels, monocytes indicate an overresponsive immune system.
The involvement of integrins to the inflammatory process is of particular interest to study co-author Kit Lam, chief of hematology and oncology with UC Davis Cancer Center.
"These two and other integrins are found on cancer cells," Lam explained. "And inflammation certainly plays a role in the onset, progression and maintenance of certain cancers. This outcome could have a huge impact on our work in finding medications that halt or at least reduce the impact of inflammation on this disease."
Takada and his colleagues will next be working to screen for molecules that block the binding of sPLA2-IIA to integrins and show that this blockage is enough to shut down an unwanted inflammatory response.
"We cannot ignore integrins anymore," Takada said. "More basic research is needed to understand how integrin-binding results in pro-inflammatory signals. We have to continue to better understand the integrin signaling process if we are to find more potential drug targets for the treatment of inflammation."
|Contact: Karen Finney|
University of California - Davis - Health System