Published in the April 28, 2005 issue of the journal Nature, the study in mice and lab cultures of immune cells called macrophages showed that a protein called I-kappa-B kinase alpha (IKKa) is responsible for terminating an inflammatory response before it can damage cells and organs.
Senior author Michael Karin, Ph.D., UCSD professor of pharmacology, explained that IKKa is part of a sophisticated two-punch system that maintains a proper inflammatory response. While it is well known that IKKa's sister protein, IKK beta (IKKb), initiates the inflammatory response, little was known about the mechanism for stopping the response before it injures tissue, such as the damage that occurs in chronic bacterial and parasitic infections like tuberculosis and leprosy, or in autoimmune disorders like rheumatoid arthritis, multiple sclerosis, and systemic lupus erythematosus (SLE).
Karin's team, which was the first to identify the IKK protein complex in 1996, determined in this new investigation that both IKKa and IKKb are activated at the same time following a microbial infection. While IKKb initiates the inflammatory response by causing the degradation of inhibitory proteins called IkBs, IKKa interacts with two additional proteins RelA and C-Rel which move into the nucleus of the cell after the IkBs are degraded. After being "tagged" by IKKa in the cytoplasm of the cell, RelA and c-Rel bind to genes that mediate the inflammatory response. But their life is limited the IKKa-mediated "tag" ensures that RelA and c-Rel will bind to their target genes for only a short duration. Once RelA and c-Rel are removed from their target
Contact: Sue Pondrom
University of California - San Diego