Related resources
Search for item elsewhere
University researcher(s)
Academic department(s)
Ca2+ stores and Ca2+ entry differentially contribute to the release of IL-1 beta and IL-1 alpha from murine macrophages.
Brough D, Le Feuvre R, Wheeler R, Solovyova N, Hilfiker S, Rothwell NJ, Verkhratsky A
J Immunol. 2003;170( 6):3029-36.
Access to files
Full-text and supplementary files are not available from Manchester eScholar. Use our list of Related resources to find this item elsewhere. Alternatively, request a copy from the Library's Document supply service.
Abstract
Interleukin-1 is a primary mediator of immune responses to injury and infection, but the mechanism of its cellular release is unknown. IL-1 exists as two agonist forms (IL-1 alpha and IL-1 beta) present in the cytosol of activated monocytes/macrophages. IL-1 beta is synthesized as an inactive precursor that lacks a signal sequence, and its trafficking does not use the classical endoplasmic reticulum-Golgi route of secretion. Using primary cultured murine peritoneal macrophages, we demonstrate that P2X7 receptor activation causes release of IL-1 beta and IL-1 alpha via a common pathway, dependent upon the release of Ca(2+) from endoplasmic reticulum stores and caspase-1 activity. Increases in intracellular Ca(2+) alone do not promote IL-1 secretion because a concomitant efflux of K(+) through the plasmalemma is required. In addition, we demonstrate the existence of an alternative pathway for the secretion of IL-1 alpha, independent of P2X7 receptor activation, but dependent upon Ca(2+) influx. The identification of these mechanisms provides insight into the mechanism of IL-1 secretion, and may lead to the identification of targets for the therapeutic modulation of IL-1 action in inflammation.
Keyword(s)
Animals; Cells, Cultured; Comparative Study; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; Support, Non-U.S. Gov't; immunology: Biological Transport; immunology: Intracellular Fluid; immunology: Macrophages, Peritoneal; immunology: Protein Processing, Post-Translational; metabolism: Calcium; metabolism: Potassium; pharmacology: Lipopolysaccharides; physiology: Adenosine Triphosphate; physiology: Receptors, Purinergic P2; secretion: Interleukin-1; secretion: Protein Isoforms