Autoinflammatory diseases treatment comes closer to reality

Researchers have discovered a new signaling pathway in sterile inflammation that could impact the treatment of diseases such as cancer, multiple sclerosis and rheumatoid arthritis.

Their findings offer insight into the role that activation of interferon-regulatory factor 1 (IRF1), a protein that functions as a transcriptional activator of a variety of target genes, plays in the production of chemokines and the recruitment of mononuclear cells to sites of sterile inflammation.

In this study, investigators Tomasz Kordula, Ph.D., and Sarah Spiegel, Ph.D., members of the Cancer Cell Signaling research program at Massey and professors in the Department of Biochemistry and Molecular Biology at the VCU School Medicine, found a new signaling pathway that links IL-1 to IRF1 in sterile inflammation.

IL-1, a key regulator of sterile inflammation, governs immune and inflammatory responses and has an important role in autoinflammatory diseases. IL-1 signaling triggers a process called polyubiquitination. Polyubiquitination is important to a variety of cellular functions.

While one form of polyubiquitination has been called the "kiss of death" because it targets proteins for degradation, another form known as K63-linked polyubiquitination is important to cell signaling.

Kordula said that as IRF1 affects the development of autoinflammatory diseases, targeting this previously unrecognized IL-1-induced cascade may be clinically important in the future.

The study has been published in the journal Nature Immunology.