Inflammation refers to our body’s immune response against things that harm, such as infections, toxins and injuries, in an attempt to heal itself. During inflammation, white blood cells release molecules that raise blood flow to the site of infection or injury. In addition to protecting our body, it is increasingly recognised that uncontrolled inflammation can have unwanted side effects. For example, there is now convincing evidence that ‘residual’ inflammation contributes to atherosclerosis, just as systemic inflammation is a key factor contributing to the potentially lethal outcome of sepsis.
We recently identified that in lab models of systemic inflammation, cell-to-cell communication in arteries is altered due to the formation of a previously unknown molecule (called “cis-WOOH”) which lowers blood pressure by oxidation of a protein called protein kinase G 1α (PKG1α). We hypothesise that there are important targets of cis-WOOH other than PKG1α.
This project uses a unique proteomics approach to identify additional targets involved in cis-WOOH-mediated cell-to-cell communication. We have now identified over 100 candidate proteins as selective targets of cis-WOOH. Some of these targets are 'drugable' and hence may provide the basis of novel treatments of inflammatory diseases including atherosclerosis and sepsis. The project will validate candidate proteins identified in our screen and determine how cis-WOOH-induced protein modifications regulate cell-to-cell signalling in different inflammatory diseases.