Understanding the Mechanism of IL-1β Secretion

Overview

Journal Cytokine Growth Factor Rev

Date 2011 Oct 25

PMID 22019906

Citations 641

Authors

Gloria Lopez-Castejon

David Brough

Affiliations

Soon will be listed here.

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.

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References

Verhoef P, Kertesy S, Lundberg K, Kahlenberg J, Dubyak G . Inhibitory effects of chloride on the activation of caspase-1, IL-1beta secretion, and cytolysis by the P2X7 receptor. J Immunol. 2005; 175(11):7623-34. DOI: 10.4049/jimmunol.175.11.7623. View

Boyden E, Dietrich W . Nalp1b controls mouse macrophage susceptibility to anthrax lethal toxin. Nat Genet. 2006; 38(2):240-4. DOI: 10.1038/ng1724. View

Black R, Kronheim S, Cantrell M, Deeley M, March C, Prickett K . Generation of biologically active interleukin-1 beta by proteolytic cleavage of the inactive precursor. J Biol Chem. 1988; 263(19):9437-42. View

Laliberte R, Eggler J, Gabel C . ATP treatment of human monocytes promotes caspase-1 maturation and externalization. J Biol Chem. 1999; 274(52):36944-51. DOI: 10.1074/jbc.274.52.36944. View

Dancourt J, Barlowe C . Protein sorting receptors in the early secretory pathway. Annu Rev Biochem. 2010; 79:777-802. DOI: 10.1146/annurev-biochem-061608-091319. View

Nickel W, Rabouille C . Mechanisms of regulated unconventional protein secretion. Nat Rev Mol Cell Biol. 2009; 10(2):148-55. DOI: 10.1038/nrm2617. View

Franchi L, Chen G, Marina-Garcia N, Abe A, Qu Y, Bao S . Calcium-independent phospholipase A2 beta is dispensable in inflammasome activation and its inhibition by bromoenol lactone. J Innate Immun. 2010; 1(6):607-17. PMC: 2768374. DOI: 10.1159/000227263. View

Amer A, Franchi L, Kanneganti T, Body-Malapel M, Ozoren N, Brady G . Regulation of Legionella phagosome maturation and infection through flagellin and host Ipaf. J Biol Chem. 2006; 281(46):35217-23. DOI: 10.1074/jbc.M604933200. View

Hornung V, Bauernfeind F, Halle A, Samstad E, Kono H, Rock K . Silica crystals and aluminum salts activate the NALP3 inflammasome through phagosomal destabilization. Nat Immunol. 2008; 9(8):847-56. PMC: 2834784. DOI: 10.1038/ni.1631. View

10.

Miao E, Leaf I, Treuting P, Mao D, Dors M, Sarkar A . Caspase-1-induced pyroptosis is an innate immune effector mechanism against intracellular bacteria. Nat Immunol. 2010; 11(12):1136-42. PMC: 3058225. DOI: 10.1038/ni.1960. View

11.

Thornberry N, Bull H, Calaycay J, Chapman K, Howard A, Kostura M . A novel heterodimeric cysteine protease is required for interleukin-1 beta processing in monocytes. Nature. 1992; 356(6372):768-74. DOI: 10.1038/356768a0. View

12.

Franchi L, Stoolman J, Kanneganti T, Verma A, Ramphal R, Nunez G . Critical role for Ipaf in Pseudomonas aeruginosa-induced caspase-1 activation. Eur J Immunol. 2007; 37(11):3030-9. DOI: 10.1002/eji.200737532. View

13.

Brough D, Rothwell N . Caspase-1-dependent processing of pro-interleukin-1beta is cytosolic and precedes cell death. J Cell Sci. 2007; 120(Pt 5):772-81. DOI: 10.1242/jcs.03377. View

14.

Le Feuvre R, Brough D, Iwakura Y, Takeda K, Rothwell N . Priming of macrophages with lipopolysaccharide potentiates P2X7-mediated cell death via a caspase-1-dependent mechanism, independently of cytokine production. J Biol Chem. 2001; 277(5):3210-8. DOI: 10.1074/jbc.M104388200. View

15.

Schroder K, Tschopp J . The inflammasomes. Cell. 2010; 140(6):821-32. DOI: 10.1016/j.cell.2010.01.040. View

16.

Martinon F, Petrilli V, Mayor A, Tardivel A, Tschopp J . Gout-associated uric acid crystals activate the NALP3 inflammasome. Nature. 2006; 440(7081):237-41. DOI: 10.1038/nature04516. View

17.

Lindemann S, Tolley N, Dixon D, McIntyre T, Prescott S, Zimmerman G . Activated platelets mediate inflammatory signaling by regulated interleukin 1beta synthesis. J Cell Biol. 2001; 154(3):485-90. PMC: 2196422. DOI: 10.1083/jcb.200105058. View

18.

Stinchcombe J, Griffiths G . Regulated secretion from hemopoietic cells. J Cell Biol. 1999; 147(1):1-6. PMC: 2164988. DOI: 10.1083/jcb.147.1.1. View

19.

Fernandes-Alnemri T, Yu J, Datta P, Wu J, Alnemri E . AIM2 activates the inflammasome and cell death in response to cytoplasmic DNA. Nature. 2009; 458(7237):509-13. PMC: 2862225. DOI: 10.1038/nature07710. View

20.

Stehlik C . Multiple interleukin-1beta-converting enzymes contribute to inflammatory arthritis. Arthritis Rheum. 2009; 60(12):3524-30. PMC: 2835694. DOI: 10.1002/art.24961. View