Role of the p40phox subunit in the sustained activation of neutrophil NADPH oxidase during inflammation

Arthritis is a common degenerative disease of the joints. In rheumatoid arthritis, degeneration is caused by the release of toxic substances from a type of white blood cell called a neutrophil. These toxic substances are unavoidable because they are also the substances that kill bacteria and other harmful microbes. Resting neutrophils do not produce these toxic substances until stimulated to do so (e.g. the appearance of bacteria) and then stop once the bacteria are eliminated. In the case of rheumatoid arthritis, neutrophils are constantly producing these toxic molecules. We will be trying to find ways to turn off the prolonged production of these toxic molecules that damages the joints, without compromising their production when needed to eliminate invaders like bacteria. To do this I will be investigating the role of a protein called p40-phox, in the prolonged production of the cartilage damaging toxic substances. The aim of the project is to determine if inhibiting p40-phox would make a suitable treatment for rheumatoid arthritis patients.