Mechanisms of unconventional secretion of IL-1 family cytokines.
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.
Institute for Molecular Bioscience, The University of Queensland, St Lucia 4072, Australia.
Mercedes
M
Monteleone
Institute for Molecular Bioscience, The University of Queensland, St Lucia 4072, Australia.
Jennifer L
JL
Stow
Institute for Molecular Bioscience, The University of Queensland, St Lucia 4072, Australia. Electronic address: K.Schroder@imb.uq.edu.au.
Kate
K
Schroder
D000544:Alzheimer Disease / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D000818:Animals; D001168:Arthritis / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D020170:Caspase 1 / Q000276:immunology* / Q000378:metabolism; D006073:Gout / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D006801:Humans; D053583:Interleukin-1beta / Q000276:immunology* / Q000378:metabolism; D008264:Macrophages / Q000276:immunology* / Q000378:metabolism / Q000473:pathology
C508585:IL1B protein, human; D053583:Interleukin-1beta; D020170:Caspase 1
Caspase-1; Inflammasome; Interleukin-1; Unconventional secretion