CoChat
Sign Up
Cited by 31Inflammasome and immune disordersImmune Response and InflammationInflammation biomarkers and pathways

NLRP3 inflammasome as therapeutic targets in inflammatory diseases

Open access
Prakash, Annamneedi Venkata, Park, Il-Ho, Park, Jun Woo, Bae, Jae Pil, Lee, Geum Seon, Kang, Tae Jin·2023·Biomolecules & Therapeutics
DOI 10.4062/biomolther.2023.099PMC PMC10315342
Open this paper in CoChat — free accountOpen PDF

Abstract

Innate immunity is a first line defence system in the body which is for sensing signals of danger such as pathogenic microbes or host-derived signals of cellular stress. Pattern recognition receptors (PRR's), which present in the cell memebrane, are suspect the infection through pathogen-associated molecular patterns (PAMP), and activate innate immunity with response to promote inflammation via inflammatory cells such as macrophages and neutrophils, and cytokines. Inflammasome are protein complexes which are part of innate immunity in inflammation to remove pathogens and repair damaged tissues. What is the important role of inflammation in disease? In this review, we are focused on the action mechanism of NLRP3 inflammasome in inflammatory diseases such as asthma, atopic dermatitis, and sepsis.

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.4062/biomolther.2023.099

Cites

3 of 3 references verified0 citation errors · 0 not checkable

Statistics

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • The main cytokines directly induced by NLRP3 activation are IL-1β, IL-18, IL-5, and IL-31, which are associated with the Th2 response.

    “The main cytokines directly induced by NLRP3 activation are IL-1β, IL-18, IL-5, and IL-31, which are associated with the Th2 response.68”

    From Update on the pathogenesis of atopic dermatitis. (2024) · cites this paper as [68]

    The Conclusion and the 'Atopic dermatitis and NLRP3' section say NLRP3 activation leads to release of IL-1β and IL-18. The latter section associates IL-5 and IL-31 with Th2-cell secretion, but does not say they are directly induced by NLRP3 activation. No page numbers are available in our copy. (LLM, conf=0.90)

    Experimental — accuracy not yet measured

  • NLRP3 formation is related to staphylococcal toxin and house dust mite allergens.

    “NLRP3 is the main inflammasome studied in AD; its formation is related to staphylococcal toxin and house dust mite allergens.”

    From Update on the pathogenesis of atopic dermatitis. (2024) · cites this paper as [68]

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Cites

Flagged first, then by citations

Research works printed but not linked: 64

  1. Arend W. P. Palmer G. Gabay C. 2008 IL-1, IL-18, and IL-33 families of cytokines Immunol. Rev. 223 20 38 10.1111/j.1600-065X.2008.00624.x 18613828 · DOI
  2. Bauer C. Duewell P. Mayer C. Lehr H. A. Fitzgerald K. A. Dauer M. Tschopp J. Endres S. Latz E. Schnurr M. 2010 Colitis induced in mice with dextran sulfate sodium (DSS) is mediated by the NLRP3 inflammasome Gut 59 1192 1199 10.1136/gut.2009.197822 20442201 · DOI
  3. Bauernfeind F. Ablasser A. Bartok E. Kim S. Schmid-Burgk J. Cavlar T. Hornung V. 2011a Inflammasomes: current understanding and open questions Cell. Mol. Life Sci. 68 765 783 10.1007/s00018-010-0567-4 21072676 PMC11114650 · DOI
  4. Bauernfeind F. Bartok E. Rieger A. Franchi L. Núñez G. Hornung V. 2011b Cutting edge: reactive oxygen species inhibitors block priming, but not activation, of the NLRP3 inflammasome J. Immunol. 187 613 617 10.4049/jimmunol.1100613 21677136 PMC3131480 · DOI · Paper page
  5. Bauernfeind F. G. Horvath G. Stutz A. Alnemri E. S. MacDonald K. Speert D. Fernandes-Alnemri T. Wu J. Monks B. G. Fitzgerald K. A. Hornung V. Latz E. 2009 Cutting edge: NF-kappaB activating pattern recognition and cytokine receptors license NLRP3 inflammasome activation by regulating NLRP3 expression J. Immunol. 183 787 791 10.4049/jimmunol.0901363 19570822 PMC2824855 · DOI
  6. Bel E. H. 2013 Clinical practice. Mild asthma N. Engl. J. Med. 369 549 557 10.1056/NEJMcp1214826 23924005 · DOI
  7. Bergsbaken T. Fink S. L. Cookson B. T. 2009 Pyroptosis: host cell death and inflammation Nat. Rev. Microbiol. 7 99 109 10.1038/nrmicro2070 19148178 PMC2910423 · DOI
  8. Besnard A. G. Guillou N. Tschopp J. Erard F. Couillin I. Iwakura Y. Quesniaux V. Ryffel B. Togbe D. 2011 NLRP3 inflammasome is required in murine asthma in the absence of aluminum adjuvant Allergy 66 1047 1057 10.1111/j.1398-9995.2011.02586.x 21443539 · DOI
  9. Bivik C. Verma D. Winge M. C. Lieden A. Bradley M. Rosdahl I. Söderkvist P. 2013 Genetic variation in the inflammasome and atopic dermatitis susceptibility J. Invest. Dermatol. 133 2486 2489 10.1038/jid.2013.168 23563199 · DOI
  10. Boguniewicz M. Leung D. Y. 2010 Recent insights into atopic dermatitis and implications for management of infectious complications J. Allergy Clin. Immunol. 125 4 13 10.1016/j.jaci.2009.11.027 20109729 PMC2814072 · DOI
  11. Brandt E. B. Sivaprasad U. 2011 Th2 cytokines and atopic dermatitis J. Clin. Cell. Immunol. 2 110 10.4172/2155-9899.1000110 21994899 PMC3189506 · DOI
  12. Chanez P. 2005 Severe asthma is an epithelial disease Eur. Respir. J. 25 945 946 10.1183/09031936.05.00038605 15929944 · DOI
  13. Coll R. C. Robertson A. Butler M. Cooper M. O'Neill L. A. 2011 The cytokine release inhibitory drug CRID3 targets ASC oligomerisation in the NLRP3 and AIM2 inflammasomes PLoS One 6 e29539 10.1371/journal.pone.0029539 ed2df02dd6da4d1aa07f6cc150804fbc 22216309 PMC3245271 · DOI
  14. Davies D. E. 2009 The role of the epithelium in airway remodeling in asthma Proc. Am. Thorac. Soc. 6 678 682 10.1513/pats.200907-067DP 20008875 PMC2797070 · DOI
  15. Denes A. Lopez-Castejon G. Brough D. 2012 Caspase-1: is IL-1 just the tip of the ICEberg? Cell Death Dis. 3 e338 10.1038/cddis.2012.86 22764097 PMC3406585 · DOI
  16. dos Santos C. C. 2012 The role of the inflammasome in ventilator-induced lung injury Am. J. Respir. Crit. Care Med. 185 1141 1144 10.1164/rccm.201204-0649ED 22661520 · DOI
  17. Fu Y. Wang Y. Du L. Xu C. Cao J. Fan T. Liu J. Su X. Fan S. Liu Q. Fan F. 2013 Resveratrol inhibits ionising irradiation-induced inflammation in MSCs by activating SIRT1 and limiting NLRP-3 inflammasome activation Int. J. Mol. Sci. 14 14105 14118 10.3390/ijms140714105 5211154dca064060a055145404bb90e4 23880858 PMC3742234 · DOI
  18. Gross O. Thomas C. Guarda G. Tschopp J. 2011 The inflammasome: an integrated view Immunol. Rev. 243 136 151 10.1111/j.1600-065X.2011.01046.x 21884173 · DOI · Paper page
  19. Hoffman H. M. Mueller J. L. Broide D. H. Wanderer A. A. Kolodner R. D. 2001 Mutation of a new gene encoding a putative pyrin-like protein causes familial cold autoinflammatory syndrome and Muckle-Wells syndrome Nat. Genet. 29 301 305 10.1038/ng756 11687797 PMC4322000 · DOI
  20. Holgate S. T. Roberts G. Arshad H. S. Howarth P. H. Davies D. E. 2009 The role of the airway epithelium and its interaction with environmental factors in asthma pathogenesis Proc. Am. Thorac. Soc. 6 655 659 10.1513/pats.200907-072DP 20008870 · DOI
  21. Holgate S. T. 2000 Epithelial damage and response Clin. Exp. Allergy 30 Suppl 1 37 41 10.1046/j.1365-2222.2000.00095.x 10849473 · DOI
  22. Hornung V. Bauernfeind F. Halle A. Samstad E. O. Kono H. Rock K. L. Fitzgerald K. A. Latz E. 2008 Silica crystals and aluminum salts activate the NALP3 inflammasome through phagosomal destabilization Nat. Immunol. 9 847 856 10.1038/ni.1631 18604214 PMC2834784 · DOI · Paper page
  23. Huang Y. Jiang H. Chen Y. Wang X. Yang Y. Tao J. Deng X. Liang G. Zhang H. Jiang W. Zhou R. 2018 Tranilast directly targets NLRP3 to treat inflammasome-driven diseases EMBO Mol. Med. 10 e8689 10.15252/emmm.201708689 ec29081353024f058b1f7bb888706528 29531021 PMC5887903 · DOI
  24. Jang H. Y. Koo J. H. Lee S. M. Park B. H. 2018 Atopic dermatitis-like skin lesions are suppressed in fat-1 transgenic mice through the inhibition of inflammasomes Exp. Mol. Med. 50 1 9 10.1038/s12276-018-0104-3 0101c1dc156f473cada9b2d1b02772c4 29899324 PMC6001487 · DOI
  25. Jiao D. Wong C. K. Qiu H. N. Dong J. Cai Z. Chu M. Hon K. L. Tsang M. S. Lam C. W. 2016 NOD2 and TLR2 ligands trigger the activation of basophils and eosinophils by interacting with dermal fibroblasts in atopic dermatitis-like skin inflammation Cell. Mol. Immunol. 13 535 550 10.1038/cmi.2015.77 26388234 PMC4947824 · DOI
  26. Kabashima K. 2013 New concept of the pathogenesis of atopic dermatitis: interplay among the barrier, allergy, and pruritus as a trinity J. Dermatol. Sci. 70 3 11 10.1016/j.jdermsci.2013.02.001 23473856 · DOI
  27. Kamo N. Ke B. Ghaffari A. A. Shen X. D. Busuttil R. W. Cheng G. Kupiec-Weglinski J. W. 2013 ASC/caspase-1/IL-1β signaling triggers inflammatory responses by promoting HMGB1 induction in liver ischemia/reperfusion injury Hepatology 58 351 362 10.1002/hep.26320 23408710 PMC3679353 · DOI
  28. Kanneganti T. D. Ozören N. Body-Malapel M. Amer A. Park J. H. Franchi L. Whitfield J. Barchet W. Colonna M. Vandenabeele P. Bertin J. Coyle A. Grant E. P. Akira S. Núñez G. 2006 Bacterial RNA and small antiviral compounds activate caspase-1 through cryopyrin/Nalp3 Nature 440 233 236 10.1038/nature04517 16407888 · DOI
  29. Kayagaki N. Stowe I. B. Lee B. L. O'Rourke K. Anderson K. Warming S. Cuellar T. Haley B. Roose-Girma M. Phung Q. T. Liu P. S. Lill J. R. Li H. Wu J. Kummerfeld S. Zhang J. Lee W. P. Snipas S. J. Salvesen G. S. Morris L. X. Fitzgerald L. Zhang Y. Bertram E. M. Goodnow C. C. Dixit V. M. 2015 Caspase-11 cleaves gasdermin D for non-canonical inflammasome signalling Nature 526 666 671 10.1038/nature15541 26375259 · DOI · Paper page
  30. Kesavardhana S. Kanneganti T. D. 2017 Mechanisms governing inflammasome activation, assembly and pyroptosis induction Int. Immunol. 29 201 210 10.1093/intimm/dxx018 28531279 PMC5890894 · DOI
  31. Lambrecht B. N. Hammad H. 2003 Taking our breath away: dendritic cells in the pathogenesis of asthma Nat. Rev. Immunol. 3 994 1003 10.1038/nri1249 14647481 · DOI
  32. Lambrecht B. N. Hammad H. 2012 The airway epithelium in asthma Nat. Med. 18 684 692 10.1038/nm.2737 22561832 · DOI
  33. Land W. G. 2013 Transfusion-related acute lung injury: the work of DAMPs Transfus. Med. Hemother. 40 3 13 10.1159/000345688 23637644 PMC3636009 · DOI
  34. Liang Y. Chang C. Lu Q. 2016 The genetics and epigenetics of atopic dermatitis-filaggrin and other polymorphisms Clin. Rev. Allergy Immunol. 51 315 328 10.1007/s12016-015-8508-5 26385242 · DOI
  35. Liu W. Guo W. Wu J. Luo Q. Tao F. Gu Y. Shen Y. Li J. Tan R. Xu Q. Sun Y. 2013 A novel benzo[d]imidazole derivate prevents the development of dextran sulfate sodium-induced murine experimental colitis via inhibition of NLRP3 inflammasome Biochem. Pharmacol. 85 1504 1512 10.1016/j.bcp.2013.03.008 23506741 · DOI
  36. Luo Y. P. Jiang L. Kang K. Fei D. S. Meng X. L. Nan C. C. Pan S. H. Zhao M. R. Zhao M. Y. 2014 Hemin inhibits NLRP3 inflammasome activation in sepsis-induced acute lung injury, involving heme oxygenase-1 Int. Immunopharmacol. 20 24 32 10.1016/j.intimp.2014.02.017 24583148 · DOI
  37. Macaluso F. Nothnagel M. Parwez Q. Petrasch-Parwez E. Bechara F. G. Epplen J. T. Hoffjan S. 2007 Polymorphisms in NACHT-LRR (NLR) genes in atopic dermatitis Exp. Dermatol. 16 692 698 10.1111/j.1600-0625.2007.00589.x 17620097 · DOI
  38. Man S. M. Kanneganti T. D. 2016 Converging roles of caspases in inflammasome activation, cell death and innate immunity Nat. Rev. Immunol. 16 7 21 10.1038/nri.2015.7 26655628 PMC4915362 · DOI
  39. Mariathasan S. Monack D. M. 2007 Inflammasome adaptors and sensors: intracellular regulators of infection and inflammation Nat. Rev. Immunol. 7 31 40 10.1038/nri1997 17186029 · DOI
  40. Mariathasan S. Newton K. Monack D. M. Vucic D. French Lee W. P. Roose-Girma M. Erickson S. Dixit V. M. 2004 Differential activation of the inflammasome by caspase-1 adaptors ASC and Ipaf Nature 430 213 218 10.1038/nature02664 15190255 · DOI
  41. Marples R. R. Heaton C. L. Kligman A. M. 1973 Staphylococcus aureus in psoriasis Arch. Dermatol. 107 568 570 10.1001/archderm.1973.01620190044010 4697686 · DOI
  42. Martin G. S. Mannino D. M. Eaton S. Moss M. 2003 The epidemiology of sepsis in the United States from 1979 through 2000 N. Engl. J. Med. 348 1546 1554 10.1056/NEJMoa022139 12700374 · DOI · Paper page
  43. Martínez-Girón R. van Woerden H. C. 2010 Disruption of airway epithelium in asthma pathogenesis: are protozoa responsible? Proc. Am. Thorac. Soc. 7 161 10.1513/pats.7.2.161a 20427612 · DOI
  44. Martinon F. Burns K. Tschopp J. 2002 The inflammasome: a molecular platform triggering activation of inflammatory caspases and processing of proIL-beta Mol. Cell 10 417 426 10.1016/S1097-2765(02)00599-3 12191486 · DOI · Paper page
  45. Masters S. L. Simon A. Aksentijevich I. Kastner D. L. 2009 Horror autoinflammaticus: the molecular pathophysiology of autoinflammatory disease (*) Annu. Rev. Immunol. 27 621 668 10.1146/annurev.immunol.25.022106.141627 19302049 PMC2996236 · DOI
  46. Muñoz-Planillo R. Franchi L. Miller L. S. Núñez G. 2009 A critical role for hemolysins and bacterial lipoproteins in Staphylococcus aureus-induced activation of the Nlrp3 inflammasome J. Immunol. 183 3942 3948 10.4049/jimmunol.0900729 19717510 PMC2762867 · DOI
  47. Nathan C. 2002 Points of control in infl ammation Nature 420 846 852 10.1038/nature01320 12490957 · DOI · Paper page
  48. Niebuhr M. Baumert K. Heratizadeh A. Satzer I. Werfel T. 2014 Imparied NLRP3 inflammasome expression and function in atopic dermatitis due to Th2 milieu Allergy 69 1058 1067 10.1111/all.12428 24894535 · DOI
  49. Perregaux D. Gabel C. A. 1994 Interleukin-1 beta maturation and release in response to ATP and nigericin. Evidence that potassium depletion mediated by these agents is a necessary and common feature of their activity J. Biol. Chem. 269 15195 15203 10.1016/S0021-9258(17)36591-2 8195155 · DOI
  50. Rankin J. A. 2004 Biological mediators of acute inflammation AACN Clin. Issues 15 3 17 10.1097/00044067-200401000-00002 14767362 · DOI
  51. Shi J. Zhao Y. Wang K. Shi X. Wang Y. Huang H. Zhuang Y. Cai T. Wang F. Shao F. 2015 Cleavage of GSDMD by inflammatory caspases determines pyroptotic cell death Nature 526 660 665 10.1038/nature15514 26375003 · DOI · Paper page
  52. Shimada K. Crother T. R. Karlin J. Dagvadorj J. Chiba N. Chen S. Ramanujan V. K. Wolf A. J. Vergnes L. Ojcius D. M. Rentsendorj A. Vargas M. Guerrero C. Wang Y. Fitzgerald K. A. Underhill D. M. Town T. Arditi M. 2012 Oxidized mitochondrial DNA activates the NLRP3 inflammasome during apoptosis Immunity 36 401 414 10.1016/j.immuni.2012.01.009 22342844 PMC3312986 · DOI · Paper page
  53. Soumelis V. Reche P. A. Kanzler H. Yuan W. Edward G. Homey B. Gilliet M. Ho S. Antonenko S. Lauerma A. Smith K. Gorman D. Zurawski S. Abrams J. Menon S. McClanahan T. de Waal-Malefyt Rd R. Bazan F. Kastelein R. A. Liu Y. J. 2002 Human epithelial cells trigger dendritic cell mediated allergic inflammation by producing TSLP Nat. Immunol. 3 673 680 10.1038/ni805 12055625 · DOI
  54. Tanaka H. Miyazaki N. Oashi K. Teramoto S. Shiratori M. Hashimoto M. Ohmichi M. Abe S. 2001 IL-18 might reflect disease activity in mild and moderate asthma exacerbation J. Allergy Clin. Immunol. 107 331 336 10.1067/mai.2001.112275 11174201 · DOI
  55. Tsai T. Chiang K. Hung J. Chang W. Lin H. Shien J. Chong I. Hsu Y. 2018 Der f1 induces pyroptosis in human bronchial epithelia via the NLRP3 inflammasome Int. J. Mol. Med. 41 757 764 10.3892/ijmm.2017.3310 29207030 PMC5752164 · DOI
  56. Tomi N. S. Kränke B. Aberer E. 2005 Staphylococcal toxins in patients with psoriasis, atopic dermatitis, and erythroderma, and in healthy control subjects J. Am. Acad. Dermatol. 53 67 72 10.1016/j.jaad.2005.02.034 15965423 · DOI
  57. van de Veerdonk F. L. Netea M. G. Dinarello C. A. Joosten L. A. 2011 Inflammasome activation and IL-1β and IL-18 processing during infection Trends Immunol. 32 110 116 10.1016/j.it.2011.01.003 21333600 · DOI
  58. Whelan R. Kim C. Chen M. Leiter J. Grunstein M. M. Hakonarson H. 2004 Role and regulation of interleukin-1 molecules in pro-asthmatic sensitised airway smooth muscle Eur. Respir. J. 24 559 567 10.1183/09031936.04.00133803 15459133 · DOI
  59. Willingham S. B. Allen I. C. Bergstralh D. T. Brickey W. J. Huang M. T. Taxman D. J. Duncan J. A. Ting J. P. 2009 NLRP3 (NALP3, Cryopyrin) facilitates in vivo caspase-1 activation, necrosis, and HMGB1 release via inflammasome-dependent and -independent pathways J. Immunol. 183 2008 2015 10.4049/jimmunol.0900138 19587006 PMC3652593 · DOI
  60. Wilson K. P. Black J. A. Thomson J. A. Kim E. E. Griffith J. P. Navia M. A. Murcko M. A. Chambers S. P. Aldape R. A. Raybuck S. A. Livingston D. J. 1994 Structure and mechanism of interleukin-1 beta converting enzyme Nature 370 270 275 10.1038/370270a0 8035875 · DOI
  61. Yeretssian G. Labbé K. Saleh M. 2008 Molecular regulation of inflammation and cell death Cytokine 43 380 390 10.1016/j.cyto.2008.07.015 18703350 · DOI
  62. Yin H. Li X. Yuan B. Zhang B. Hu S. Gu H. Jin X. Zhu J. 2011 Heme oxygenase-1 ameliorates LPS-induced acute lung injury correlated with downregulation of interleukin-33 Int. Immunopharmacol. 11 2112 2117 10.1016/j.intimp.2011.09.004 21945667 · DOI
  63. Zhang Q. Fan H. W. Zhang J. Z. Wang Y. M. Xing H. J. 2015 NLRP3 rs35829419 polymorphism is associated with increased susceptibility to multiple diseases in humans Genet. Mol. Res. 14 13968 13980 10.4238/2015.October.29.17 26535712 · DOI
  64. Zhou R. Tardivel A. Thorens B. Choi I. Tschopp J. 2010 Thioredoxin-interacting protein links oxidative stress to inflammasome activation Nat. Immunol. 11 136 140 10.1038/ni.1831 20023662 · DOI · Paper page

Cited by

Sorted by citations

Authors
Prakash, A. V., Park, I.-H., Park, J. W., Bae, J. P., Lee, G. S., & Kang, T. J.
Affiliations
Sahmyook University (KR)
Corresponding author
Kang, Tae Jin
ORCID
Park, Il-Ho
Venue
Biomolecules & Therapeutics
Publisher
The Korean Society of Applied Pharmacology
Published
2023-07-01
Volume
31
Issue
4
Pages
395-401
ISSN
  • 1976-9148 (ISSN-L)
  • 2005-4483
DOI
10.4062/biomolther.2023.099
PMC
PMC10315342
OpenAlex
W4382344668
Cited by
31
References
3
Citations by year
2026: 7 · 2025: 10 · 2024: 12 · 2023: 2
FWCI
0.82
Type
journal article
Language
en
Open access
Licence
Locations
  • Biomolecules & Therapeutics (publishedVersion, cc-by-nc)
  • PubMed Central (publishedVersion, cc-by-nc)
  • PubMed (publishedVersion)
Funders
Academic Research Fund
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Inflammasome and immune disorders
  • Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
  • Life Sciences › Immunology and Microbiology › Immunology › Inflammation biomarkers and pathways
Keywords
NLRP3 inflammasome, inflammatory diseases, innate immunity, pattern recognition receptors, pathogen-associated molecular patterns, macrophages, neutrophils, cytokines, asthma, atopic dermatitis, sepsis, therapeutic target

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review