| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
and IL-1
from Murine Macrophages1
School of Biological Sciences, University of Manchester, Manchester, United Kingdom
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
and IL-1
) present in the cytosol of activated monocytes/macrophages. IL-1 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 and IL-1 via a common pathway, dependent upon the release of Ca2+ from endoplasmic reticulum stores and caspase-1 activity. Increases in intracellular Ca2+ 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, independent of P2X7 receptor activation, but dependent upon Ca2+ 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.
This article has been cited by other articles:
|
|
 |
|
  J. Chu, L. M. Thomas, S. C. Watkins, L. Franchi, G. Nunez, and R. D. Salter Cholesterol-dependent cytolysins induce rapid release of mature IL-1{beta} from murine macrophages in a NLRP3 inflammasome and cathepsin B-dependent manner J. Leukoc. Biol., November 1, 2009; 86(5): 1227 - 1238. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. Pelegrin, C. Barroso-Gutierrez, and A. Surprenant P2X7 Receptor Differentially Couples to Distinct Release Pathways for IL-1{beta} in Mouse Macrophage J. Immunol., June 1, 2008; 180(11): 7147 - 7157. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Qu, L. Franchi, G. Nunez, and G. R. Dubyak Nonclassical IL-1beta Secretion Stimulated by P2X7 Receptors Is Dependent on Inflammasome Activation and Correlated with Exosome Release in Murine Macrophages J. Immunol., August 1, 2007; 179(3): 1913 - 1925. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. Brough and N. J. Rothwell Caspase-1-dependent processing of pro-interleukin-1beta is cytosolic and precedes cell death J. Cell Sci., March 1, 2007; 120(5): 772 - 781. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Stock, T. Schilling, A. Schwab, and C. Eder Lysophosphatidylcholine Stimulates IL-1beta Release from Microglia via a P2X7 Receptor-Independent Mechanism J. Immunol., December 15, 2006; 177(12): 8560 - 8568. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Wimmer, S. K. Khaldoyanidi, M. Judex, N. Serobyan, R. G. DiScipio, and I. U. Schraufstatter CCL18/PARC stimulates hematopoiesis in long-term bone marrow cultures indirectly through its effect on monocytes Blood, December 1, 2006; 108(12): 3722 - 3729. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 V. H. J. Roberts, S. L. Greenwood, A. C. Elliott, C. P. Sibley, and L. H. Waters Purinergic receptors in human placenta: evidence for functionally active P2X4, P2X7, P2Y2, and P2Y6 Am J Physiol Regulatory Integrative Comp Physiol, May 1, 2006; 290(5): R1374 - R1386. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Yao, M. R. Karabasil, N. Purwanti, X. Li, T. Akamatsu, N. Kanamori, and K. Hosoi Tissue Kallikrein mK13 Is a Candidate Processing Enzyme for the Precursor of Interleukin-1beta in the Submandibular Gland of Mice J. Biol. Chem., March 24, 2006; 281(12): 7968 - 7976. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Okemoto, K. Kawasaki, K. Hanada, M. Miura, and M. Nishijima A Potent Adjuvant Monophosphoryl Lipid A Triggers Various Immune Responses, but Not Secretion of IL-1{beta} or Activation of Caspase-1 J. Immunol., January 15, 2006; 176(2): 1203 - 1208. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Hao, X. Li, M. A. Rizzo, J. V. Rocheleau, B. M. Dawant, and D. W. Piston Regulation of two insulin granule populations within the reserve pool by distinct calcium sources J. Cell Sci., December 15, 2005; 118(24): 5873 - 5884. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. Y. A. Hemdan, F. Emmrich, K. Adham, G. Wichmann, I. Lehmann, A. El-Massry, H. Ghoneim, J. Lehmann, and U. Sack Dose-Dependent Modulation of the In Vitro Cytokine Production of Human Immune Competent Cells by Lead Salts Toxicol. Sci., July 1, 2005; 86(1): 75 - 83. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F. Bianco, E. Pravettoni, A. Colombo, U. Schenk, T. Moller, M. Matteoli, and C. Verderio Astrocyte-Derived ATP Induces Vesicle Shedding and IL-1{beta} Release from Microglia J. Immunol., June 1, 2005; 174(11): 7268 - 7277. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. C. Denlinger, G. Angelini, K. Schell, D. N. Green, A. G. Guadarrama, U. Prabhu, D. B. Coursin, P. J. Bertics, and K. Hogan Detection of Human P2X7 Nucleotide Receptor Polymorphisms by a Novel Monocyte Pore Assay Predictive of Alterations in Lipopolysaccharide-Induced Cytokine Production J. Immunol., April 1, 2005; 174(7): 4424 - 4431. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. L. Wilson, S. E. Francis, S. K. Dower, and D. C. Crossman Secretion of Intracellular IL-1 Receptor Antagonist (Type 1) Is Dependent on P2X7 Receptor Activation J. Immunol., July 15, 2004; 173(2): 1202 - 1208. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Andrei, P. Margiocco, A. Poggi, L. V. Lotti, M. R. Torrisi, and A. Rubartelli From The Cover: Phospholipases C and A2 control lysosome-mediated IL-1{beta} secretion: Implications for inflammatory processes PNAS, June 29, 2004; 101(26): 9745 - 9750. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Sluyter, A. N. Shemon, and J. S. Wiley Glu496 to Ala Polymorphism in the P2X7 Receptor Impairs ATP-Induced IL-1{beta} Release from Human Monocytes J. Immunol., March 15, 2004; 172(6): 3399 - 3405. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
