Skip to main content
Erschienen in: Journal of Clinical Immunology 5/2010

01.09.2010

The Role of the Inflammasome in Nonmyeloid Cells

verfasst von: Amir S. Yazdi, Stefan K. Drexler, Jürg Tschopp

Erschienen in: Journal of Clinical Immunology | Ausgabe 5/2010

Einloggen, um Zugang zu erhalten

Abstract

Inflammasomes are cytosolic multiprotein complexes that can proteolytically activate caspase-1. Activated caspase-1 is needed for the maturation and secretion of interleukin (IL)-1β and IL-18. In the past decade, there has been tremendous progress in our knowledge of inflammasome function and IL-1 signaling, mainly in cells of the innate immune system, such as monocytes, macrophages, neutrophils, and dendritic cells. Because nonimmune cells, including keratinocytes, synovial cells, or astrocytes, can form an interface between the body and the environment or a defined compartment (brain, joint), they are important guardians for the detection of danger signals and the consecutive initiation of an inflammatory response. They are present in anatomical compartments that are less accessible to myeloid cells and thus can fulfill tasks usually performed by residential macrophages. This review focuses on recent progress in our understanding of the processing and functional role of IL-1 in epithelial, mesenchymal, and neuronal cells and in conditions such as tissue repair.
Literatur
1.
Zurück zum Zitat Auron PE, Webb AC, Rosenwasser LJ, et al. Nucleotide sequence of human monocyte interleukin 1 precursor cDNA. Proc Natl Acad Sci USA. 1984;81:7907–11.CrossRefPubMed Auron PE, Webb AC, Rosenwasser LJ, et al. Nucleotide sequence of human monocyte interleukin 1 precursor cDNA. Proc Natl Acad Sci USA. 1984;81:7907–11.CrossRefPubMed
2.
Zurück zum Zitat Lomedico PT, Gubler U, Hellmann CP, et al. Cloning and expression of murine interleukin-1 cDNA in Escherichia coli. Nature. 1984;312:458–62.CrossRefPubMed Lomedico PT, Gubler U, Hellmann CP, et al. Cloning and expression of murine interleukin-1 cDNA in Escherichia coli. Nature. 1984;312:458–62.CrossRefPubMed
3.
Zurück zum Zitat Ogilvie AC, Hack CE, Wagstaff J, et al. IL-1 beta does not cause neutrophil degranulation but does lead to IL-6, IL-8, and nitrite/nitrate release when used in patients with cancer. J Immunol. 1996;156:389–94.PubMed Ogilvie AC, Hack CE, Wagstaff J, et al. IL-1 beta does not cause neutrophil degranulation but does lead to IL-6, IL-8, and nitrite/nitrate release when used in patients with cancer. J Immunol. 1996;156:389–94.PubMed
4.
Zurück zum Zitat Tewari A, Buhles Jr WC, Starnes Jr HF. Preliminary report: effects of interleukin-1 on platelet counts. Lancet. 1990;336:712–4.CrossRefPubMed Tewari A, Buhles Jr WC, Starnes Jr HF. Preliminary report: effects of interleukin-1 on platelet counts. Lancet. 1990;336:712–4.CrossRefPubMed
5.
Zurück zum Zitat Kavita U, Mizel SB. Differential sensitivity of interleukin-1 alpha and -beta precursor proteins to cleavage by calpain, a calcium-dependent protease. J Biol Chem. 1995;270:27758–65.CrossRefPubMed Kavita U, Mizel SB. Differential sensitivity of interleukin-1 alpha and -beta precursor proteins to cleavage by calpain, a calcium-dependent protease. J Biol Chem. 1995;270:27758–65.CrossRefPubMed
6.
Zurück zum Zitat Thornberry NA, Bull HG, Calaycay JR, et al. A novel heterodimeric cysteine protease is required for interleukin-1 beta processing in monocytes. Nature. 1992;356:768–74.CrossRefPubMed Thornberry NA, Bull HG, Calaycay JR, et al. A novel heterodimeric cysteine protease is required for interleukin-1 beta processing in monocytes. Nature. 1992;356:768–74.CrossRefPubMed
7.
Zurück zum Zitat Martinon F, Mayor A, Tschopp J. The inflammasomes: guardians of the body. Annu Rev Immunol. 2009;27:229–65.CrossRefPubMed Martinon F, Mayor A, Tschopp J. The inflammasomes: guardians of the body. Annu Rev Immunol. 2009;27:229–65.CrossRefPubMed
8.
Zurück zum Zitat Dostert C, Meylan E, Tschopp J. Intracellular pattern-recognition receptors. Adv Drug Deliv Rev. 2008;60:830–40.CrossRefPubMed Dostert C, Meylan E, Tschopp J. Intracellular pattern-recognition receptors. Adv Drug Deliv Rev. 2008;60:830–40.CrossRefPubMed
9.
Zurück zum Zitat Yazdi AS, Guarda G, D'Ombrain MC, Drexler SK. Inflammatory caspases in innate immunity and inflammation. J Innate Immun. 2010;2:228–37. Yazdi AS, Guarda G, D'Ombrain MC, Drexler SK. Inflammatory caspases in innate immunity and inflammation. J Innate Immun. 2010;2:228–37.
10.
Zurück zum Zitat Meylan E, Tschopp J, Karin M. Intracellular pattern recognition receptors in the host response. Nature. 2006;442:39–44.CrossRefPubMed Meylan E, Tschopp J, Karin M. Intracellular pattern recognition receptors in the host response. Nature. 2006;442:39–44.CrossRefPubMed
11.
Zurück zum Zitat Bos JD, Zonneveld I, Das PK, Krieg SR, van der Loos CM, Kapsenberg ML. The skin immune system (SIS): distribution and immunophenotype of lymphocyte subpopulations in normal human skin. J Invest Dermatol. 1987;88:569–73.CrossRefPubMed Bos JD, Zonneveld I, Das PK, Krieg SR, van der Loos CM, Kapsenberg ML. The skin immune system (SIS): distribution and immunophenotype of lymphocyte subpopulations in normal human skin. J Invest Dermatol. 1987;88:569–73.CrossRefPubMed
12.
Zurück zum Zitat Lebre MC, van der Aar AM, van Baarsen L, et al. Human keratinocytes express functional Toll-like receptor 3, 4, 5, and 9. J Invest Dermatol. 2007;127:331–41.CrossRefPubMed Lebre MC, van der Aar AM, van Baarsen L, et al. Human keratinocytes express functional Toll-like receptor 3, 4, 5, and 9. J Invest Dermatol. 2007;127:331–41.CrossRefPubMed
13.
Zurück zum Zitat Miller LS, Modlin RL. Human keratinocyte Toll-like receptors promote distinct immune responses. J Invest Dermatol. 2007;127:262–3.CrossRefPubMed Miller LS, Modlin RL. Human keratinocyte Toll-like receptors promote distinct immune responses. J Invest Dermatol. 2007;127:262–3.CrossRefPubMed
14.
Zurück zum Zitat Watanabe H, Gaide O, Petrilli V, et al. Activation of the IL-1beta-processing inflammasome is involved in contact hypersensitivity. J Invest Dermatol. 2007;127:1956–63.CrossRefPubMed Watanabe H, Gaide O, Petrilli V, et al. Activation of the IL-1beta-processing inflammasome is involved in contact hypersensitivity. J Invest Dermatol. 2007;127:1956–63.CrossRefPubMed
15.
Zurück zum Zitat Feldmeyer L, Keller M, Niklaus G, Hohl D, Werner S, Beer HD. The inflammasome mediates UVB-induced activation and secretion of interleukin-1beta by keratinocytes. Curr Biol. 2007;17:1140–5.CrossRefPubMed Feldmeyer L, Keller M, Niklaus G, Hohl D, Werner S, Beer HD. The inflammasome mediates UVB-induced activation and secretion of interleukin-1beta by keratinocytes. Curr Biol. 2007;17:1140–5.CrossRefPubMed
16.
Zurück zum Zitat Sutterwala FS, Ogura Y, Szczepanik M, et al. Critical role for NALP3/CIAS1/Cryopyrin in innate and adaptive immunity through its regulation of caspase-1. Immunity. 2006;24:317–27.CrossRefPubMed Sutterwala FS, Ogura Y, Szczepanik M, et al. Critical role for NALP3/CIAS1/Cryopyrin in innate and adaptive immunity through its regulation of caspase-1. Immunity. 2006;24:317–27.CrossRefPubMed
17.
Zurück zum Zitat Johansen C, Moeller K, Kragballe K, Iversen L. The activity of caspase-1 is increased in lesional psoriatic epidermis. J Invest Dermatol. 2007;127:2857–64.PubMed Johansen C, Moeller K, Kragballe K, Iversen L. The activity of caspase-1 is increased in lesional psoriatic epidermis. J Invest Dermatol. 2007;127:2857–64.PubMed
18.
Zurück zum Zitat Jin Y, Birlea SA, Fain PR, Spritz RA. Genetic variations in NALP1 are associated with generalized vitiligo in a Romanian population. J Invest Dermatol. 2007;127:2558–62.CrossRefPubMed Jin Y, Birlea SA, Fain PR, Spritz RA. Genetic variations in NALP1 are associated with generalized vitiligo in a Romanian population. J Invest Dermatol. 2007;127:2558–62.CrossRefPubMed
19.
Zurück zum Zitat Jin Y, Mailloux CM, Gowan K, et al. NALP1 in vitiligo-associated multiple autoimmune disease. N Engl J Med. 2007;356:1216–25.CrossRefPubMed Jin Y, Mailloux CM, Gowan K, et al. NALP1 in vitiligo-associated multiple autoimmune disease. N Engl J Med. 2007;356:1216–25.CrossRefPubMed
20.
Zurück zum Zitat Li WW, Guo TZ, Liang D, et al. The NALP1 inflammasome controls cytokine production and nociception in a rat fracture model of complex regional pain syndrome. Pain. 2009;147:277–86.CrossRefPubMed Li WW, Guo TZ, Liang D, et al. The NALP1 inflammasome controls cytokine production and nociception in a rat fracture model of complex regional pain syndrome. Pain. 2009;147:277–86.CrossRefPubMed
21.
Zurück zum Zitat Keller M, Ruegg A, Werner S, Beer HD. Active caspase-1 is a regulator of unconventional protein secretion. Cell. 2008;132:818–31.CrossRefPubMed Keller M, Ruegg A, Werner S, Beer HD. Active caspase-1 is a regulator of unconventional protein secretion. Cell. 2008;132:818–31.CrossRefPubMed
22.
Zurück zum Zitat Rawat R, Cohen TV, Ampong B et al. Inflammasome up-regulation and activation in dysferlin-deficient skeletal muscle. Am J Pathol. 2010;176(6):2891–900. Rawat R, Cohen TV, Ampong B et al. Inflammasome up-regulation and activation in dysferlin-deficient skeletal muscle. Am J Pathol. 2010;176(6):2891–900.
23.
Zurück zum Zitat Gasse P, Mary C, Guenon I, et al. IL-1R1/MyD88 signaling and the inflammasome are essential in pulmonary inflammation and fibrosis in mice. J Clin Invest. 2007;117:3786–99.PubMed Gasse P, Mary C, Guenon I, et al. IL-1R1/MyD88 signaling and the inflammasome are essential in pulmonary inflammation and fibrosis in mice. J Clin Invest. 2007;117:3786–99.PubMed
24.
Zurück zum Zitat Gasse P, Riteau N, Charron S, et al. Uric acid is a danger signal activating NALP3 inflammasome in lung injury inflammation and fibrosis. Am J Respir Crit Care Med. 2009;179:903–13.CrossRefPubMed Gasse P, Riteau N, Charron S, et al. Uric acid is a danger signal activating NALP3 inflammasome in lung injury inflammation and fibrosis. Am J Respir Crit Care Med. 2009;179:903–13.CrossRefPubMed
25.
Zurück zum Zitat Kolly L, Karababa M, Joosten LA, et al. Inflammatory role of ASC in antigen-induced arthritis is independent of caspase-1, NALP-3, and IPAF. J Immunol. 2009;183:4003–12.CrossRefPubMed Kolly L, Karababa M, Joosten LA, et al. Inflammatory role of ASC in antigen-induced arthritis is independent of caspase-1, NALP-3, and IPAF. J Immunol. 2009;183:4003–12.CrossRefPubMed
26.
Zurück zum Zitat Abbate A, Salloum FN, Vecile E, et al. Anakinra, a recombinant human interleukin-1 receptor antagonist, inhibits apoptosis in experimental acute myocardial infarction. Circulation. 2008;117:2670–83.CrossRefPubMed Abbate A, Salloum FN, Vecile E, et al. Anakinra, a recombinant human interleukin-1 receptor antagonist, inhibits apoptosis in experimental acute myocardial infarction. Circulation. 2008;117:2670–83.CrossRefPubMed
27.
Zurück zum Zitat Suzuki K, Murtuza B, Smolenski RT, et al. Overexpression of interleukin-1 receptor antagonist provides cardioprotection against ischemia-reperfusion injury associated with reduction in apoptosis. Circulation. 2001;104:1308–13.CrossRef Suzuki K, Murtuza B, Smolenski RT, et al. Overexpression of interleukin-1 receptor antagonist provides cardioprotection against ischemia-reperfusion injury associated with reduction in apoptosis. Circulation. 2001;104:1308–13.CrossRef
28.
Zurück zum Zitat Drexler SK, Foxwell BM. The role of toll-like receptors in chronic inflammation. Int J Biochem Cell Biol. 2010;42:506–18. Drexler SK, Foxwell BM. The role of toll-like receptors in chronic inflammation. Int J Biochem Cell Biol. 2010;42:506–18.
29.
Zurück zum Zitat Drexler SK, Kong P, Inglis J et al. SIGIRR/TIR8 is an inhibitor of TLR signalling in primary human cells and regulates inflammation in models of rheumatoid arthritis. Arthritis Rheum. 2010. doi:10.1002/art.27517. Drexler SK, Kong P, Inglis J et al. SIGIRR/TIR8 is an inhibitor of TLR signalling in primary human cells and regulates inflammation in models of rheumatoid arthritis. Arthritis Rheum. 2010. doi:10.​1002/​art.​27517.
30.
Zurück zum Zitat Drexler SK, Kong PL, Wales J, Foxwell BM. Cell signalling in macrophages, the principal innate immune effector cells of rheumatoid arthritis. Arthritis Res Ther. 2008;10:216.CrossRefPubMed Drexler SK, Kong PL, Wales J, Foxwell BM. Cell signalling in macrophages, the principal innate immune effector cells of rheumatoid arthritis. Arthritis Res Ther. 2008;10:216.CrossRefPubMed
31.
Zurück zum Zitat Lossinsky AS, Shivers RR. Structural pathways for macromolecular and cellular transport across the blood–brain barrier during inflammatory conditions. Histol Histopathol. 2004;19:535–64. Review.PubMed Lossinsky AS, Shivers RR. Structural pathways for macromolecular and cellular transport across the blood–brain barrier during inflammatory conditions. Histol Histopathol. 2004;19:535–64. Review.PubMed
32.
Zurück zum Zitat Miyake T, Hattori T, Fukuda M, Kitamura T, Fujita S. Quantitative studies on proliferative changes of reactive astrocytes in mouse cerebral cortex. Brain Res. 1988;451:133–8.CrossRefPubMed Miyake T, Hattori T, Fukuda M, Kitamura T, Fujita S. Quantitative studies on proliferative changes of reactive astrocytes in mouse cerebral cortex. Brain Res. 1988;451:133–8.CrossRefPubMed
33.
Zurück zum Zitat Herx LM, Rivest S, Yong VW. Central nervous system-initiated inflammation and neurotrophism in trauma: IL-1 beta is required for the production of ciliary neurotrophic factor. J Immunol. 2000;165:2232–9.PubMed Herx LM, Rivest S, Yong VW. Central nervous system-initiated inflammation and neurotrophism in trauma: IL-1 beta is required for the production of ciliary neurotrophic factor. J Immunol. 2000;165:2232–9.PubMed
34.
Zurück zum Zitat Neven B, Callebaut I, Prieur AM, et al. Molecular basis of the spectral expression of CIAS1 mutations associated with phagocytic cell-mediated autoinflammatory disorders CINCA/NOMID, MWS, and FCU. Blood. 2004;103:2809–15.CrossRefPubMed Neven B, Callebaut I, Prieur AM, et al. Molecular basis of the spectral expression of CIAS1 mutations associated with phagocytic cell-mediated autoinflammatory disorders CINCA/NOMID, MWS, and FCU. Blood. 2004;103:2809–15.CrossRefPubMed
35.
Zurück zum Zitat Apelt J, Schliebs R. Beta-amyloid-induced glial expression of both pro- and anti-inflammatory cytokines in cerebral cortex of aged transgenic Tg2576 mice with Alzheimer plaque pathology. Brain Res. 2001;894:21–30.CrossRefPubMed Apelt J, Schliebs R. Beta-amyloid-induced glial expression of both pro- and anti-inflammatory cytokines in cerebral cortex of aged transgenic Tg2576 mice with Alzheimer plaque pathology. Brain Res. 2001;894:21–30.CrossRefPubMed
36.
Zurück zum Zitat Ona VO, Li M, Vonsattel JP, et al. Inhibition of caspase-1 slows disease progression in a mouse model of Huntington's disease. Nature. 1999;399:263–7.CrossRefPubMed Ona VO, Li M, Vonsattel JP, et al. Inhibition of caspase-1 slows disease progression in a mouse model of Huntington's disease. Nature. 1999;399:263–7.CrossRefPubMed
37.
Zurück zum Zitat Parish CL, Finkelstein DI, Tripanichkul W, Satoskar AR, Drago J, Horne MK. The role of interleukin-1, interleukin-6, and glia in inducing growth of neuronal terminal arbors in mice. J Neurosci. 2002;22:8034–41.PubMed Parish CL, Finkelstein DI, Tripanichkul W, Satoskar AR, Drago J, Horne MK. The role of interleukin-1, interleukin-6, and glia in inducing growth of neuronal terminal arbors in mice. J Neurosci. 2002;22:8034–41.PubMed
38.
Zurück zum Zitat Halle A, Hornung V, Petzold GC, et al. The NALP3 inflammasome is involved in the innate immune response to amyloid-beta. Nat Immunol. 2008;9:857–65.CrossRefPubMed Halle A, Hornung V, Petzold GC, et al. The NALP3 inflammasome is involved in the innate immune response to amyloid-beta. Nat Immunol. 2008;9:857–65.CrossRefPubMed
39.
Zurück zum Zitat de Rivero Vaccari JP, Lotocki G, Marcillo AE, Dietrich WD, Keane RW. A molecular platform in neurons regulates inflammation after spinal cord injury. J Neurosci. 2008;28:3404–14.CrossRefPubMed de Rivero Vaccari JP, Lotocki G, Marcillo AE, Dietrich WD, Keane RW. A molecular platform in neurons regulates inflammation after spinal cord injury. J Neurosci. 2008;28:3404–14.CrossRefPubMed
40.
Zurück zum Zitat Yin Y, Yan Y, Jiang X, et al. Inflammasomes are differentially expressed in cardiovascular and other tissues. Int J Immunopathol Pharmacol. 2009;22:311–22.PubMed Yin Y, Yan Y, Jiang X, et al. Inflammasomes are differentially expressed in cardiovascular and other tissues. Int J Immunopathol Pharmacol. 2009;22:311–22.PubMed
Metadaten
Titel
The Role of the Inflammasome in Nonmyeloid Cells
verfasst von
Amir S. Yazdi
Stefan K. Drexler
Jürg Tschopp
Publikationsdatum
01.09.2010
Verlag
Springer US
Erschienen in
Journal of Clinical Immunology / Ausgabe 5/2010
Print ISSN: 0271-9142
Elektronische ISSN: 1573-2592
DOI
https://doi.org/10.1007/s10875-010-9437-y

Weitere Artikel der Ausgabe 5/2010

Journal of Clinical Immunology 5/2010 Zur Ausgabe

Leitlinien kompakt für die Innere Medizin

Mit medbee Pocketcards sicher entscheiden.

Seit 2022 gehört die medbee GmbH zum Springer Medizin Verlag

Echinokokkose medikamentös behandeln oder operieren?

06.05.2024 DCK 2024 Kongressbericht

Die Therapie von Echinokokkosen sollte immer in spezialisierten Zentren erfolgen. Eine symptomlose Echinokokkose kann – egal ob von Hunde- oder Fuchsbandwurm ausgelöst – konservativ erfolgen. Wenn eine Op. nötig ist, kann es sinnvoll sein, vorher Zysten zu leeren und zu desinfizieren. 

Wo hapert es noch bei der Umsetzung der POMGAT-Leitlinie?

03.05.2024 DCK 2024 Kongressbericht

Seit November 2023 gibt es evidenzbasierte Empfehlungen zum perioperativen Management bei gastrointestinalen Tumoren (POMGAT) auf S3-Niveau. Vieles wird schon entsprechend der Empfehlungen durchgeführt. Wo es im Alltag noch hapert, zeigt eine Umfrage in einem Klinikverbund.

Das Risiko für Vorhofflimmern in der Bevölkerung steigt

02.05.2024 Vorhofflimmern Nachrichten

Das Risiko, im Lauf des Lebens an Vorhofflimmern zu erkranken, ist in den vergangenen 20 Jahren gestiegen: Laut dänischen Zahlen wird es drei von zehn Personen treffen. Das hat Folgen weit über die Schlaganfallgefährdung hinaus.

VHF-Ablation nützt wohl nur bei reduzierter Auswurfleistung

02.05.2024 Ablationstherapie Nachrichten

Ob die Katheterablation von Vorhofflimmern bei Patienten mit Herzinsuffizienz die Komplikationsraten senkt, scheint davon abzuhängen, ob die Auswurfleistung erhalten ist oder nicht. Das legen die Ergebnisse einer Metaanalyse nahe.

Update Innere Medizin

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.