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Understanding the mechanism of IL-1β secretion

https://doi.org/10.1016/j.cytogfr.2011.10.001Get rights and content
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Abstract

The cytokine interleukin-1β (IL-1β) is a key mediator of the inflammatory response. Essential for the host-response and resistance to pathogens, it also exacerbates damage during chronic disease and acute tissue injury. It is not surprising therefore that there is a huge level of interest in how this protein is produced and exported from cells. However, the mechanism of IL-1β release has proven to be elusive. It does not follow the conventional ER-Golgi route of secretion. A literature full of disparate observations arising from numerous experimental systems, has contributed to a complicated mix of diverse proposals. Here we summarise these observations and propose that secretion of IL-1β occurs on a continuum, dependent upon stimulus strength and the extracellular IL-1β requirement.

Keywords

IL-1β
Caspase-1
Inflammation
Golgi
Cell death

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Gloria Lopez-Castejon is a Research Associate at the University of Manchester, UK. She completed her PhD at the University of Murcia, Spain in 2007 investigating the mechanisms of secretion of IL-1β in teleost fish. Since 2007 she has studied the contribution of macrophages to inflammation, and in particular the regulation of IL-1 production.

David Brough is a Wellcome Trust Career Development Research Fellow at the University of Manchester, UK. He completed his PhD at the University of Manchester in 2002 investigating the purinergic control of IL-1β secretion from microglia. Between 2002 and 2005 he worked as a postdoctoral research associate at the University of Cambridge investigating cell signalling mechanisms controlled by inositol lipids and soluble inositol phosphates. In 2005 he returned to Manchester, initially as a postdoc until 2008 when he was awarded his fellowship. His lab is focused on understanding the initiation of inflammation following injury, and how the key pro-inflammatory cytokine IL-1β is secreted from the cell.