Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.


Logo for

PNAS 101 (26): 9745-9750

Copyright © 2004 by the National Academy of Sciences.

From The Cover


Phospholipases C and A2 control lysosome-mediated IL-1{beta} secretion: Implications for inflammatory processes

Cristina Andrei *, Paola Margiocco *, Alessandro Poggi {dagger}, Lavinia V. Lotti {ddagger}, M. R. Torrisi {ddagger}, and Anna Rubartelli *, §

*Cell Transport Unit and {dagger}Laboratory of Immunology, Department of Oncogenesis, National Cancer Research Institute, 16132 Genoa, Italy; and {ddagger}Department of Experimental Medicine and Pathology, University of Rome La Sapienza, 00161 Rome, Italy

Edited by Charles A. Dinarello, University of Colorado Health Sciences Center, Denver, CO, and approved May 12, 2004

Received for publication December 23, 2003.

Abstract: Blocking the activity of IL-1{beta} has entered the clinical arena of treating autoimmune diseases. However, a successful outcome of this approach requires a clear definition of the mechanisms controlling IL-1{beta} release. These are still unclear as IL-1{beta}, lacking a secretory signal peptide, follows a nonclassical pathway of secretion. Here, we analyze the molecular mechanism(s) undergoing IL-1{beta} processing and release in human monocytes and provide a unifying model for the regulated secretion of the cytokine. Our data show that in a first step, pro-caspase-1 and endotoxin-induced pro-IL-1{beta} are targeted in part to specialized secretory lysosomes, where they colocalize with other lysosomal proteins. Externalization of mature IL-1{beta} and caspase-1 together with lysosomal proteins is then facilitated by extracellular ATP. ATP triggers the efflux of K+ from the cell, followed by Ca2+ influx and activation of three phospholipases: phosphatidylcholine-specific phospholipase C and calcium-independent and -dependent phospholipase A2. Whereas calcium-independent phospholipase A2 is involved in processing, phosphatidylcholine-specific phospholipase C and calcium-dependent phospholipase A2 are required for secretion. Dissection of the events that follow ATP triggering allowed to demonstrate that K+ efflux is responsible for phosphatidylcholine-specific phospholipase C induction, which in turn allows the rise in intracellular free calcium concentration required for activation of phospholipase A2. This activation is ultimately responsible for lysosome exocytosis and IL-1{beta} secretion.

This paper was submitted directly (Track II) to the PNAS office.

Abbreviations: [Ca2+]i, intracellular free calcium concentration; PLC, phospholipase C; PC-PLC, phosphatidylcholine-specific PLC; PLD, phospholipase D; iPLA2, calcium-independent phospholipase A2; cPLA2, calcium-dependent phospholipase A2; LPS, lipopolysaccharide; AACOCF3, arachidonyl trifluoromethylketone; ac-YVAD-cmk, acetyl-Tyr-Val-Ala-Aspchloromethyl ketone; LDH, lactate dehydrogenase.

§ To whom correspondence should be addressed. E-mail: anna.rubartelli{at}

© 2004 by The National Academy of Sciences of the USA

Nucleotide receptor P2RX7 stimulation enhances LPS-induced interferon-{beta} production in murine macrophages.
M. L. Gavala, Y.- P. Liu, L. Y. Lenertz, L. Zeng, J. B. Blanchette, A. G. Guadarrama, L. C. Denlinger, P. J. Bertics, and J. A. Smith (2013)
J. Leukoc. Biol. 94, 759-768
   Abstract »    Full Text »    PDF »
Herpes Simplex Virus 1 Infection Induces Activation and Subsequent Inhibition of the IFI16 and NLRP3 Inflammasomes.
K. E. Johnson, L. Chikoti, and B. Chandran (2013)
J. Virol. 87, 5005-5018
   Abstract »    Full Text »    PDF »
The Therapeutic Potential of Modifying Inflammasomes and NOD-Like Receptors.
F. Di Virgilio (2013)
Pharmacol. Rev. 65, 872-905
   Abstract »    Full Text »    PDF »
Substrate and Inhibitor-induced Dimerization and Cooperativity in Caspase-1 but Not Caspase-3.
D. Datta, C. L. McClendon, M. P. Jacobson, and J. A. Wells (2013)
J. Biol. Chem. 288, 9971-9981
   Abstract »    Full Text »    PDF »
Diacylglycerol kinase inhibitor R59022 attenuates conjugated linoleic acid-mediated inflammation in human adipocytes.
K. Martinez, S. Shyamasundar, A. Kennedy, C. C. Chuang, A. Marsh, J. Kincaid, T. Reid, and M. McIntosh (2013)
J. Lipid Res. 54, 662-670
   Abstract »    Full Text »    PDF »
Diversity in unconventional protein secretion.
C. Rabouille, V. Malhotra, and W. Nickel (2012)
J. Cell Sci. 125, 5251-5255
   Full Text »    PDF »
Constitutive lysosome exocytosis releases ATP and engages P2Y receptors in human monocytes.
V. Sivaramakrishnan, S. Bidula, H. Campwala, D. Katikaneni, and S. J. Fountain (2012)
J. Cell Sci. 125, 4567-4575
   Abstract »    Full Text »    PDF »
Phosphatidylinositol 4,5-Bisphosphate (PI(4,5)P2)-dependent Oligomerization of Fibroblast Growth Factor 2 (FGF2) Triggers the Formation of a Lipidic Membrane Pore Implicated in Unconventional Secretion.
J. P. Steringer, S. Bleicken, H. Andreas, S. Zacherl, M. Laussmann, K. Temmerman, F. X. Contreras, T. A. M. Bharat, J. Lechner, H.-M. Muller, et al. (2012)
J. Biol. Chem. 287, 27659-27669
   Abstract »    Full Text »    PDF »
Toll-like receptor 5 (TLR5), IL-1{beta} secretion, and asparagine endopeptidase are critical factors for alveolar macrophage phagocytosis and bacterial killing.
D. Descamps, M. Le Gars, V. Balloy, D. Barbier, S. Maschalidi, M. Tohme, M. Chignard, R. Ramphal, B. Manoury, and J.-M. Sallenave (2012)
PNAS 109, 1619-1624
   Abstract »    Full Text »    PDF »
Microglial Ca2+-Activated K+ Channels Are Possible Molecular Targets for the Analgesic Effects of S-Ketamine on Neuropathic Pain.
Y. Hayashi, K. Kawaji, L. Sun, X. Zhang, K. Koyano, T. Yokoyama, S. Kohsaka, K. Inoue, and H. Nakanishi (2011)
J. Neurosci. 31, 17370-17382
   Abstract »    Full Text »    PDF »
IL-1{alpha} and IL-1{beta} Recruit Different Myeloid Cells and Promote Different Stages of Sterile Inflammation.
P. Rider, Y. Carmi, O. Guttman, A. Braiman, I. Cohen, E. Voronov, M. R. White, C. A. Dinarello, and R. N. Apte (2011)
J. Immunol. 187, 4835-4843
   Abstract »    Full Text »    PDF »
Ginger Phenylpropanoids Inhibit IL-1{beta} and Prostanoid Secretion and Disrupt Arachidonate-Phospholipid Remodeling by Targeting Phospholipases A2.
A. Nievergelt, J. Marazzi, R. Schoop, K.-H. Altmann, and J. Gertsch (2011)
J. Immunol. 187, 4140-4150
   Abstract »    Full Text »    PDF »
Coordinated Host Responses during Pyroptosis: Caspase-1-Dependent Lysosome Exocytosis and Inflammatory Cytokine Maturation.
T. Bergsbaken, S. L. Fink, A. B. den Hartigh, W. P. Loomis, and B. T. Cookson (2011)
J. Immunol. 187, 2748-2754
   Abstract »    Full Text »    PDF »
TpF1 from Treponema pallidum Activates Inflammasome and Promotes the Development of Regulatory T Cells.
C. Babolin, A. Amedei, D. Ozolins, A. Zilevica, M. M. D'Elios, and M. de Bernard (2011)
J. Immunol. 187, 1377-1384
   Abstract »    Full Text »    PDF »
Interleukin-1 in the pathogenesis and treatment of inflammatory diseases.
C. A. Dinarello (2011)
Blood 117, 3720-3732
   Abstract »    Full Text »    PDF »
Activation of Macrophages by P2X7-Induced Microvesicles from Myeloid Cells Is Mediated by Phospholipids and Is Partially Dependent on TLR4.
L. M. Thomas and R. D. Salter (2010)
J. Immunol. 185, 3740-3749
   Abstract »    Full Text »    PDF »
Two haplotypes of the P2X7 receptor containing the Ala-348 to Thr polymorphism exhibit a gain-of-function effect and enhanced interleukin-1{beta} secretion.
L. Stokes, S. J. Fuller, R. Sluyter, K. K. Skarratt, B. J. Gu, and J. S. Wiley (2010)
FASEB J 24, 2916-2927
   Abstract »    Full Text »    PDF »
Inflammation and insulin resistance induced by trans-10, cis-12 conjugated linoleic acid depend on intracellular calcium levels in primary cultures of human adipocytes.
A. Kennedy, K. Martinez, S. Chung, K. LaPoint, R. Hopkins, S. F. Schmidt, K. Andersen, S. Mandrup, and M. McIntosh (2010)
J. Lipid Res. 51, 1906-1917
   Abstract »    Full Text »    PDF »
Association of coagulation factor XIII-A with Golgi proteins within monocyte-macrophages: implications for subcellular trafficking and secretion.
P. A. Cordell, B. T. Kile, K. F. Standeven, E. C. Josefsson, R. J. Pease, and P. J. Grant (2010)
Blood 115, 2674-2681
   Abstract »    Full Text »    PDF »
P2X7-Dependent Release of Interleukin-1{beta} and Nociception in the Spinal Cord following Lipopolysaccharide.
A. K. Clark, A. A. Staniland, F. Marchand, T. K. Y. Kaan, S. B. McMahon, and M. Malcangio (2010)
J. Neurosci. 30, 573-582
   Abstract »    Full Text »    PDF »
Rab39a Binds Caspase-1 and Is Required for Caspase-1-dependent Interleukin-1{beta} Secretion.
C. E. Becker, E. M. Creagh, and L. A. J. O'Neill (2009)
J. Biol. Chem. 284, 34531-34537
   Abstract »    Full Text »    PDF »
Cholesterol-dependent cytolysins induce rapid release of mature IL-1{beta} from murine macrophages in a NLRP3 inflammasome and cathepsin B-dependent manner.
J. Chu, L. M. Thomas, S. C. Watkins, L. Franchi, G. Nunez, and R. D. Salter (2009)
J. Leukoc. Biol. 86, 1227-1238
   Abstract »    Full Text »    PDF »
CA-074Me Protection against Anthrax Lethal Toxin.
Z. L. Newman, S. H. Leppla, and M. Moayeri (2009)
Infect. Immun. 77, 4327-4336
   Abstract »    Full Text »    PDF »
Pro-interleukin (IL)-1{beta} Shares a Core Region of Stability as Compared with Mature IL-1{beta} While Maintaining a Distinctly Different Configurational Landscape: A COMPARATIVE HYDROGEN/DEUTERIUM EXCHANGE MASS SPECTROMETRY STUDY.
K. L. Hailey, S. Li, M. D. Andersen, M. Roy, V. L. Woods Jr, and P. A. Jennings (2009)
J. Biol. Chem. 284, 26137-26148
   Abstract »    Full Text »    PDF »
An intrinsic quality-control mechanism ensures unconventional secretion of fibroblast growth factor 2 in a folded conformation.
L. C. Torrado, K. Temmerman, H.-M. Muller, M. P. Mayer, C. Seelenmeyer, R. Backhaus, and W. Nickel (2009)
J. Cell Sci. 122, 3322-3329
   Abstract »    Full Text »    PDF »
Externalization of the Leaderless Cytokine IL-1F6 Occurs in Response to Lipopolysaccharide/ATP Activation of Transduced Bone Marrow Macrophages.
U. Martin, J. Scholler, J. Gurgel, B. Renshaw, J. E. Sims, and C. A. Gabel (2009)
J. Immunol. 183, 4021-4030
   Abstract »    Full Text »    PDF »
Biglycan, a Danger Signal That Activates the NLRP3 Inflammasome via Toll-like and P2X Receptors.
A. Babelova, K. Moreth, W. Tsalastra-Greul, J. Zeng-Brouwers, O. Eickelberg, M. F. Young, P. Bruckner, J. Pfeilschifter, R. M. Schaefer, H.-J. Grone, et al. (2009)
J. Biol. Chem. 284, 24035-24048
   Abstract »    Full Text »    PDF »
DAMPs and inflammatory processes: the role of redox in the different outcomes.
S. Carta, P. Castellani, L. Delfino, S. Tassi, R. Vene, and A. Rubartelli (2009)
J. Leukoc. Biol. 86, 549-555
   Abstract »    Full Text »    PDF »
An Integrated Transcriptomics and Proteomics Analysis of the Secretome of the Helminth Pathogen Fasciola hepatica: PROTEINS ASSOCIATED WITH INVASION AND INFECTION OF THE MAMMALIAN HOST.
M. W. Robinson, R. Menon, S. M. Donnelly, J. P. Dalton, and S. Ranganathan (2009)
Mol. Cell. Proteomics 8, 1891-1907
   Abstract »    Full Text »    PDF »
Pathogen-Induced Interleukin-1{beta} Processing and Secretion Is Regulated by a Biphasic Redox Response.
S. Tassi, S. Carta, R. Vene, L. Delfino, M. R. Ciriolo, and A. Rubartelli (2009)
J. Immunol. 183, 1456-1462
   Abstract »    Full Text »    PDF »
NLRP3/Cryopyrin Is Necessary for Interleukin-1{beta} (IL-1{beta}) Release in Response to Hyaluronan, an Endogenous Trigger of Inflammation in Response to Injury.
K. Yamasaki, J. Muto, K. R. Taylor, A. L. Cogen, D. Audish, J. Bertin, E. P. Grant, A. J. Coyle, A. Misaghi, H. M. Hoffman, et al. (2009)
J. Biol. Chem. 284, 12762-12771
   Abstract »    Full Text »    PDF »
Differential requirement for the activation of the inflammasome for processing and release of IL-1{beta} in monocytes and macrophages.
M. G. Netea, C. A. Nold-Petry, M. F. Nold, L. A. B. Joosten, B. Opitz, J. H. M. van der Meer, F. L. van de Veerdonk, G. Ferwerda, B. Heinhuis, I. Devesa, et al. (2009)
Blood 113, 2324-2335
   Abstract »    Full Text »    PDF »
The Activation of P2X7 Receptor Impairs Lysosomal Functions and Stimulates the Release of Autophagolysosomes in Microglial Cells.
T. Takenouchi, M. Nakai, Y. Iwamaru, S. Sugama, M. Tsukimoto, M. Fujita, J. Wei, A. Sekigawa, M. Sato, S. Kojima, et al. (2009)
J. Immunol. 182, 2051-2062
   Abstract »    Full Text »    PDF »
Prointerleukin-18 Is Activated by Meprin {beta} in Vitro and in Vivo in Intestinal Inflammation.
S. Banerjee and J. S. Bond (2008)
J. Biol. Chem. 283, 31371-31377
   Abstract »    Full Text »    PDF »
HMG-CoA reductase inhibition induces IL-1{beta} release through Rac1/PI3K/PKB-dependent caspase-1 activation.
L. M. Kuijk, J. M. Beekman, J. Koster, H. R. Waterham, J. Frenkel, and P. J. Coffer (2008)
Blood 112, 3563-3573
   Abstract »    Full Text »    PDF »
Cytokine secretion requires phosphatidylcholine synthesis.
Y. Tian, C. Pate, A. Andreolotti, L. Wang, E. Tuomanen, K. Boyd, E. Claro, and S. Jackowski (2008)
J. Cell Biol. 181, 945-957
   Abstract »    Full Text »    PDF »
Phosphatidylcholine-Specific Phospholipase C Activation in Epithelial Ovarian Cancer Cells.
F. Spadaro, C. Ramoni, D. Mezzanzanica, S. Miotti, P. Alberti, S. Cecchetti, E. Iorio, V. Dolo, S. Canevari, and F. Podo (2008)
Cancer Res. 68, 6541-6549
   Abstract »    Full Text »    PDF »
Lysosomes Are the Major Vesicular Compartment Undergoing Ca2+-Regulated Exocytosis from Cortical Astrocytes.
D. Li, N. Ropert, A. Koulakoff, C. Giaume, and M. Oheim (2008)
J. Neurosci. 28, 7648-7658
   Abstract »    Full Text »    PDF »
Lysophospholipids and ATP Mutually Suppress Maturation and Release of IL-1{beta} in Mouse Microglial Cells Using a Rho-Dependent Pathway.
T. Takenouchi, Y. Iwamaru, S. Sugama, M. Sato, M. Hashimoto, and H. Kitani (2008)
J. Immunol. 180, 7827-7839
   Abstract »    Full Text »    PDF »
A Key Role for Redox Signaling in Rapid P2X7 Receptor-Induced IL-1{beta} Processing in Human Monocytes.
J. Hewinson, S. F. Moore, C. Glover, A. G. Watts, and A. B. MacKenzie (2008)
J. Immunol. 180, 8410-8420
   Abstract »    Full Text »    PDF »
ATP is released by monocytes stimulated with pathogen-sensing receptor ligands and induces IL-1{beta} and IL-18 secretion in an autocrine way.
A. Piccini, S. Carta, S. Tassi, D. Lasiglie, G. Fossati, and A. Rubartelli (2008)
PNAS 105, 8067-8072
   Abstract »    Full Text »    PDF »
P2X7 Receptor Differentially Couples to Distinct Release Pathways for IL-1{beta} in Mouse Macrophage.
P. Pelegrin, C. Barroso-Gutierrez, and A. Surprenant (2008)
J. Immunol. 180, 7147-7157
   Abstract »    Full Text »    PDF »
Phosphatidylcholine-specific phospholipase C activation is required for CCR5-dependent, NF-kB-driven CCL2 secretion elicited in response to HIV-1 gp120 in human primary macrophages.
L. Fantuzzi, F. Spadaro, C. Purificato, S. Cecchetti, F. Podo, F. Belardelli, S. Gessani, and C. Ramoni (2008)
Blood 111, 3355-3363
   Abstract »    Full Text »    PDF »
Anthrax lethal toxin and Salmonella elicit the common cell death pathway of caspase-1-dependent pyroptosis via distinct mechanisms.
S. L. Fink, T. Bergsbaken, and B. T. Cookson (2008)
PNAS 105, 4312-4317
   Abstract »    Full Text »    PDF »
Innate Immune Responses to TREM-1 Activation: Overlap, Divergence, and Positive and Negative Cross-Talk with Bacterial Lipopolysaccharide.
K. Dower, D. K. Ellis, K. Saraf, S. A. Jelinsky, and L.-L. Lin (2008)
J. Immunol. 180, 3520-3534
   Abstract »    Full Text »    PDF »
Identification of a Molecular Signature in Human Type 1 Diabetes Mellitus Using Serum and Functional Genomics.
X. Wang, S. Jia, R. Geoffrey, R. Alemzadeh, S. Ghosh, and M. J. Hessner (2008)
J. Immunol. 180, 1929-1937
   Abstract »    Full Text »    PDF »
Regulation of P2X4 receptors by lysosomal targeting, glycan protection and exocytosis.
O. S. Qureshi, A. Paramasivam, J. C. H. Yu, and R. D. Murrell-Lagnado (2007)
J. Cell Sci. 120, 3838-3849
   Abstract »    Full Text »    PDF »
Nonclassical IL-1{beta} Secretion Stimulated by P2X7 Receptors Is Dependent on Inflammasome Activation and Correlated with Exosome Release in Murine Macrophages.
Y. Qu, L. Franchi, G. Nunez, and G. R. Dubyak (2007)
J. Immunol. 179, 1913-1925
   Abstract »    Full Text »    PDF »
Unconventional secretion: an extracellular trap for export of fibroblast growth factor 2.
W. Nickel (2007)
J. Cell Sci. 120, 2295-2299
   Abstract »    Full Text »    PDF »
Differential Requirement of P2X7 Receptor and Intracellular K+ for Caspase-1 Activation Induced by Intracellular and Extracellular Bacteria.
L. Franchi, T.-D. Kanneganti, G. R. Dubyak, and G. Nunez (2007)
J. Biol. Chem. 282, 18810-18818
   Abstract »    Full Text »    PDF »
Stimulation of P2 (P2X7) receptors in human dendritic cells induces the release of tissue factor-bearing microparticles.
M. Baroni, C. Pizzirani, M. Pinotti, D. Ferrari, E. Adinolfi, S. Calzavarini, P. Caruso, F. Bernardi, and F. Di Virgilio (2007)
FASEB J 21, 1926-1933
   Abstract »    Full Text »    PDF »
Stimulation of P2 receptors causes release of IL-1{beta}-loaded microvesicles from human dendritic cells.
C. Pizzirani, D. Ferrari, P. Chiozzi, E. Adinolfi, D. Sandona, E. Savaglio, and F. Di Virgilio (2007)
Blood 109, 3856-3864
   Abstract »    Full Text »    PDF »
Stressing the obvious? Cell stress and cell stress proteins in cardiovascular disease.
A. Shamaei-Tousi, J. P. Halcox, and B. Henderson (2007)
Cardiovasc Res 74, 19-28
   Abstract »    Full Text »    PDF »
Caspase-1-dependent processing of pro-interleukin-1beta is cytosolic and precedes cell death.
D. Brough and N. J. Rothwell (2007)
J. Cell Sci. 120, 772-781
   Abstract »    Full Text »    PDF »
ATP Activates a Reactive Oxygen Species-dependent Oxidative Stress Response and Secretion of Proinflammatory Cytokines in Macrophages.
C. M. Cruz, A. Rinna, H. J. Forman, A. L. M. Ventura, P. M. Persechini, and D. M. Ojcius (2007)
J. Biol. Chem. 282, 2871-2879
   Abstract »    Full Text »    PDF »
The maturation potential of NK cell clones toward autologous dendritic cells correlates with HMGB1 secretion.
C. Semino, J. Ceccarelli, L. V. Lotti, M. R. Torrisi, G. Angelini, and A. Rubartelli (2007)
J. Leukoc. Biol. 81, 92-99
   Abstract »    Full Text »    PDF »
HMGB1-secreting capacity of multiple cell lineages revealed by a novel HMGB1 ELISPOT assay.
H. Wahamaa, T. Vallerskog, S. Qin, C. Lunderius, G. LaRosa, U. Andersson, and H. E. Harris (2007)
J. Leukoc. Biol. 81, 129-136
   Abstract »    Full Text »    PDF »
Opposite Regulation of IL-1{beta} and Secreted IL-1 Receptor Antagonist Production by Phosphatidylinositide-3 Kinases in Human Monocytes Activated by Lipopolysaccharides or Contact with T Cells.
N. Molnarfi, L. Gruaz, J.-M. Dayer, and D. Burger (2007)
J. Immunol. 178, 446-454
   Abstract »    Full Text »    PDF »
Pathogenesis of familial periodic fever syndromes or hereditary autoinflammatory syndromes.
A. Simon and J. W. M. van der Meer (2007)
Am J Physiol Regulatory Integrative Comp Physiol 292, R86-R98
   Abstract »    Full Text »    PDF »
Heat Shock Protein 70 Is Secreted from Tumor Cells by a Nonclassical Pathway Involving Lysosomal Endosomes.
S. S. Mambula and S. K. Calderwood (2006)
J. Immunol. 177, 7849-7857
   Abstract »    Full Text »    PDF »
Cell-surface heparan sulfate proteoglycans are essential components of the unconventional export machinery of FGF-2.
C. Zehe, A. Engling, S. Wegehingel, T. Schafer, and W. Nickel (2006)
PNAS 103, 15479-15484
   Abstract »    Full Text »    PDF »
Novel carbohydrate-binding activity of bovine liver {beta}-glucuronidase toward lactose/N-acetyllactosamine sequences.
H. Matsushita-Oikawa, M. Komatsu, N. Iida-Tanaka, H. Sakagami, T. Kanamori, I. Matsumoto, N. Seno, and H. Ogawa (2006)
Glycobiology 16, 891-901
   Abstract »    Full Text »    PDF »
IP3Rs are sufficient for dendritic cell Ca2+ signaling in the absence of RyR1.
M. Stolk, M. Leon-Ponte, M. Merrill, G. P. Ahern, and P. J. O'Connell (2006)
J. Leukoc. Biol. 80, 651-658
   Abstract »    Full Text »    PDF »
Histone deacetylase inhibitors prevent exocytosis of interleukin-1beta-containing secretory lysosomes: role of microtubules.
S. Carta, S. Tassi, C. Semino, G. Fossati, P. Mascagni, C. A. Dinarello, and A. Rubartelli (2006)
Blood 108, 1618-1626
   Abstract »    Full Text »    PDF »
Modulation by LL-37 of the Responses of Salivary Glands to Purinergic Agonists.
S. Pochet, S. Tandel, S. Querriere, M. Tre-Hardy, M. Garcia-Marcos, M. De Lorenzi, M. Vandenbranden, A. Marino, M. Devleeschouwer, and J.-P. Dehaye (2006)
Mol. Pharmacol. 69, 2037-2046
   Abstract »    Full Text »    PDF »
The P2X7 Receptor: A Key Player in IL-1 Processing and Release.
D. Ferrari, C. Pizzirani, E. Adinolfi, R. M. Lemoli, A. Curti, M. Idzko, E. Panther, and F. Di Virgilio (2006)
J. Immunol. 176, 3877-3883
   Abstract »    Full Text »    PDF »
A novel form of immune signaling revealed by transmission of the inflammatory mediator serotonin between dendritic cells and T cells.
P. J. O'Connell, X. Wang, M. Leon-Ponte, C. Griffiths, S. C. Pingle, and G. P. Ahern (2006)
Blood 107, 1010-1017
   Abstract »    Full Text »    PDF »
A Potent Adjuvant Monophosphoryl Lipid A Triggers Various Immune Responses, but Not Secretion of IL-1{beta} or Activation of Caspase-1.
K. Okemoto, K. Kawasaki, K. Hanada, M. Miura, and M. Nishijima (2006)
J. Immunol. 176, 1203-1208
   Abstract »    Full Text »    PDF »
Inhibitory Effects of Chloride on the Activation of Caspase-1, IL-1{beta} Secretion, and Cytolysis by the P2X7 Receptor.
P. A. Verhoef, S. B. Kertesy, K. Lundberg, J. M. Kahlenberg, and G. R. Dubyak (2005)
J. Immunol. 175, 7623-7634
   Abstract »    Full Text »    PDF »
NK/iDC interaction results in IL-18 secretion by DCs at the synaptic cleft followed by NK cell activation and release of the DC maturation factor HMGB1.
C. Semino, G. Angelini, A. Poggi, and A. Rubartelli (2005)
Blood 106, 609-616
   Abstract »    Full Text »    PDF »
Astrocyte-Derived ATP Induces Vesicle Shedding and IL-1{beta} Release from Microglia.
F. Bianco, E. Pravettoni, A. Colombo, U. Schenk, T. Moller, M. Matteoli, and C. Verderio (2005)
J. Immunol. 174, 7268-7277
   Abstract »    Full Text »    PDF »
Role of interleukin-1 (IL-1) in the pathogenesis of systemic onset juvenile idiopathic arthritis and clinical response to IL-1 blockade.
V. Pascual, F. Allantaz, E. Arce, M. Punaro, and J. Banchereau (2005)
J. Exp. Med. 201, 1479-1486
   Abstract »    Full Text »    PDF »
Blocking IL-1 in systemic inflammation.
C. A. Dinarello (2005)
J. Exp. Med. 201, 1355-1359
   Abstract »    Full Text »    PDF »
Direct transport across the plasma membrane of mammalian cells of Leishmania HASPB as revealed by a CHO export mutant.
C. Stegmayer, A. Kehlenbach, S. Tournaviti, S. Wegehingel, C. Zehe, P. Denny, D. F. Smith, B. Schwappach, and W. Nickel (2005)
J. Cell Sci. 118, 517-527
   Abstract »    Full Text »    PDF »
IL-1{beta}: An endosomal exit.
M. D. Wewers (2004)
PNAS 101, 10241-10242
   Full Text »    PDF »

To Advertise     Find Products

Science Signaling. ISSN 1937-9145 (online), 1945-0877 (print). Pre-2008: Science's STKE. ISSN 1525-8882