Abstract
Alarmins, also called danger-associated molecular patterns （DAMPs）, are molecules that are rapidly released from necrotic cells. They serve as early warning signals for the surrounding cells and tissues and cause inflammatory reactions by accumulating immune cells, such as neutrophils and macrophages. This type of inflammation is called “sterile inflammation” and is not accompanied by infection with pathogenic organisms. Interleukin-1α （IL-1α） is a typical alarmin. Its precursor （pIL-1α） is synthesized inside the cell and enzymatically cleaved to generate N-terminal propiece IL-1α （ppIL-1α） and C-terminal mature IL-1α （mIL-1α）. pIL-1α and ppIL-1α are preferentially localized in the nucleus due to the presence of nuclear localizing sequence （NLS）. pIL-1α is cleaved by proteases such as calpain and secreted outside the cells where it functions as a cytokine by binding to IL-1 receptor type 1 （IL-1R1）. Interestingly, pIL-1α is also released from damaged cells and binds to the same receptor. On the other hand, both pIL-1α and ppIL-1α contribute to the transcriptional regulation of some genes in the nucleus. Hence, based on these properties, IL-1α is recognized as a dual-functional cytokine. This review summarizes recent knowledge on the role of IL-1α as an alarmin.
