Different members of the IL-1 family come out in different ways: DAMPs vs cytokines?

• Main Authors: Sonia eCarta, Rosa eLavieri, Anna eRubartelli
• Format: Article
• Language: English
• Published: Frontiers Media S.A. 2013-05-01
• Series: Frontiers in Immunology
• Subjects: TLR; IL-1β; secretion; IL-18; IL-33; IL-1α
• Online Access: http://journal.frontiersin.org/Journal/10.3389/fimmu.2013.00123/full

Intercellular communications control fundamental biological processes required for the survival of multicellular organisms. Secretory proteins are among the most important messengers in this network of information. Proteins destined to this function contain a signal sequence with the necessary information to target them to the Endoplasmic Reticulum (ER), and are released in the extracellular environment by a "classical" pathway of secretion. However, in the early 90s it became evident that non classical mechanisms must exist for the secretion of some proteins, which in spite of their extracellular localization and function, lack a signal peptide. Indeed, the group of leaderless secretory proteins rapidly grew and is still growing. Many of them are implicated in the regulation of the inflammatory response. Interestingly, most members of the IL-1 family (IL-1F), including the master pro-inflammatory cytokine IL-1β, are leaderless proteins and find their way out of the cells in different manners. In this article, we will review current hypotheses on the mechanisms of externalization of IL-1F members and discuss their relevance with respect to the different functions (as cytokines or as DAMPs) played by the different IL-1 proteins.