Inflammation: New Mechanism Discovered

Scientists affiliated with VIB and UGent in Belgium have discovered a mechanism used by the protein A20 to combat inflammation. This news is timely for those suffering from rheumatoid arthritis (RA)…Friday, October 12 is World Arthritis Day.

Rudi Beyaert, Deputy Department Director at VIB–UGent said in the October 9, 2012 news release, “We hope that our research can eventually contribute to the development of new therapies against rheumatoid arthritis and other auto-immune conditions.” Beyaert and his research team previously identified the molecule A20 as an important point of focus for the development of new medicines against RA and other autoimmune diseases. A20 appears to exert an anti-inflammatory effect in white blood cells.

Previous research has demonstrated that A20 interferes with specific “signaling pathways” in our cells that stimulate the activity of a DNA binding molecule (NF-κB). NF-κB plays a key role in many immunological processes and excessive activation of NF-κB can result in a whole range of “inflammatory diseases, ” including arthritis. However, it is still largely unknown how A20 interferes with the activity of NF-κB.

Kelly Verhelst and other scientists on the team of Rudi Beyaert have now mapped the specific interaction between A20 and the NF-κB “signaling pathway.” They demonstrated that a small particle (ZF7) at the end of the A20 protein binds to certain small molecules (ubiquitin chains), which are attached to specific NF-κB signaling proteins in the cell. This makes it impossible for these proteins to communicate with other proteins, thereby disrupting the signal that would normally result in inflammation.

Rudi Beyaert said, “Now that we know the importance of this small fragment (ZF7) of A20 for the anti-inflammatory effect, we can also use it as a point of focus for the development of medicines against various auto-immune diseases. This is one step closer, but we still have a long way to go.”