Intracellular IL-1 receptor antagonist type 1 inhibits IL-1-induced cytokine production in keratinocytes through binding to the third component of the COP9 signalosome

Interleukin-1 (IL-1) is a key driver of inflammation, and the body makes its own blocker for it: the IL-1 receptor antagonist (IL-1Ra). Most IL-1Ra works outside cells, but three of its four forms stay inside them, and what those inner forms do was unknown.

This study from the University of Colorado Health Sciences Center, co-authored by Dr. Kelly Cairns, found that the main intracellular form binds to part of a protein complex called the COP9 signalosome. Through that binding, it dampens the signaling that leads skin cells to make the inflammatory molecules IL-6 and IL-8. In other words, IL-1Ra can also fight inflammation from inside the cell.

Citation: Banda NK, Guthridge C, Sheppard D, Cairns KS, Muggli M, Bech-Otschir D, Dubiel W, Arend WP. Intracellular IL-1 receptor antagonist type 1 inhibits IL-1-induced cytokine production in keratinocytes through binding to the third component of the COP9 signalosome. Journal of Immunology. 2005;174(6):3608–16. doi:10.4049/jimmunol.174.6.3608

👉 Read the article in the Journal of Immunology