Acaspase activates secretion of many inflammatory response proteins without signal sequences, say Martin Keller, Hans-Dietmar Beer, and colleagues (Swiss Federal Institute of Technology, Zürich, Switzerland), revealing a new pathway for secretion.
The cytokine interleukin-1α (IL-1α) has no secretion signal peptide but is nonetheless secreted as part of the inflammatory response. IL-1α is also not a substrate for caspase-1, but its secretion is reduced in macrophages that do not express the protease.
In the new work, the authors showed that caspase-1 inhibition reduced secretion of IL-1α and almost 80 other inflammatory response proteins, many of which lack secretion signal peptides, including FGF-2. Many of the transported proteins were not caspase-1 substrates, yet catalytic activity of the enzyme was required for their secretion, for reasons that are not yet clear. Both IL-1α and FGF-2 bound to caspase-1, suggesting that the enzyme may carry them directly.
“Unlike signal sequence–driven secretion, which is regulated at the level of transcription,” says Beer, “unconventional secretion can rapidly release a wide variety of proteins.” The proteins involved trigger detoxification, tissue repair, and cell survival, suggesting caspase-1 is helping to regulate the entire inflammatory response. 
