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Cytokine. 2015 Aug;74(2):213-8. doi: 10.1016/j.cyto.2015.03.022. Epub 2015 Apr 25.

Mechanisms of unconventional secretion of IL-1 family cytokines.

Author information

1
Institute for Molecular Bioscience, The University of Queensland, St Lucia 4072, Australia.
2
Institute for Molecular Bioscience, The University of Queensland, St Lucia 4072, Australia. Electronic address: K.Schroder@imb.uq.edu.au.

Abstract

One of the most poorly understood processes in cell biology is the peculiar ability of specific leaderless proteins to be secreted via ER/Golgi-independent mechanisms ('unconventional protein secretion'). One such leaderless protein is the major immune-activating cytokine, interleukin-1β (IL-1β). Unusual amongst cytokines, IL-1β is expressed in the cytosol as an inactive precursor protein. It requires maturation by the caspase-1 protease, which itself requires activation upon immune cell sensing of infection or cell stress. Despite 25 years of intensive research into IL-1β secretory mechanisms, how it exits the cell is still not well understood. Here we will review the various mechanisms by which macrophages have been proposed to secrete IL-1 family cytokines, and the potential involvement of caspase-1 therein. Since aberrant IL-1β production drives inherited and acquired human diseases (e.g. autoinflammatory diseases, arthritic diseases, gout, Alzheimer's disease), elucidation of the IL-1β secretory pathway may offer new therapeutic opportunities for treatment across this wide range of human conditions.

KEYWORDS:

Caspase-1; Inflammasome; Interleukin-1; Unconventional secretion

PMID:
25922276
DOI:
10.1016/j.cyto.2015.03.022
[Indexed for MEDLINE]

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