nach oben

Erschienen in:

04.09.2020 | Original Research Paper

IL-33 enhances macrophage release of IL-1β and promotes pain and inflammation in gouty arthritis

verfasst von: Victor Fattori, Larissa Staurengo-Ferrari, Tiago H. Zaninelli, Rubia Casagrande, Rene D. Oliveira, Paulo Louzada-Junior, Thiago M. Cunha, Jose C. Alves-Filho, Mauro M. Teixeira, Fernando Q. Cunha, Flavio A. Amaral, Waldiceu A. Verri Jr

Erschienen in: Inflammation Research | Ausgabe 12/2020

Einloggen, um Zugang zu erhalten

Abstract

Objective

To investigate the role of IL-33 in gouty arthritis.

Material

174 Balb/c (wild-type) and 54 ST2^−/− mice were used in this study. In vitro experiments were conducted in bone marrow-derived macrophages (BMDMs). Synovial fluid samples from gouty arthritis (n = 7) and osteoarthritis (n = 8) hospital patients were used to measure IL-33 and sST2 levels.

Methods

Gout was induced by injection of monosodium urate (MSU) crystals in the knee joint of mice. Pain was determined using the electronic von Frey and static weight bearing. Neutrophil recruitment was determined by H&E staining, Rosenfeld staining slides, and MPO activity. ELISA was used for cytokine and sST2 measurement. The priming effect of IL-33 was determined in BMDM.

Results

Synovial fluid of gout patients showed higher IL-33 levels and neutrophil counts than osteoarthritis patients. In mice, the absence of ST2 prevented mechanical pain, knee joint edema, neutrophil recruitment to the knee joint, and lowered IL-1β and superoxide anion levels. In macrophages, IL-33 enhanced the release of IL-1β and TNF-α, and BMDMs from ST2^−/− showed reduced levels of these cytokines after stimulus with MSU crystals.

Conclusion

IL-33 mediates gout pain and inflammation by boosting macrophages production of cytokines upon MSU crystals stimulus.

Rees F, Hui M, Doherty M. Optimizing current treatment of gout. Nat Rev Rheumatol. 2014;10(5):271–83.PubMed

Fattori V, Amaral FA, Verri WA Jr. Neutrophils and arthritis: Role in disease and pharmacological perspectives. Pharmacol Res. 2016;112:84–988.PubMed

Dalbeth, N.; Merriman, T. R.; Stamp, L. K., Gout. The Lancet2016, 388, (10055), 2039–2052.

Martinon F, Petrilli V, Mayor A, Tardivel A, Tschopp J. Gout-associated uric acid crystals activate the NALP3 inflammasome. Nature. 2006;440(7081):237–41.PubMed

Amaral FA, Costa VV, Tavares LD, Sachs D, Coelho FM, Fagundes CT, Soriani FM, Silveira TN, Cunha LD, Zamboni DS, Quesniaux V, Peres RS, Cunha TM, Cunha FQ, Ryffel B, Souza DG, Teixeira MM. NLRP3 inflammasome-mediated neutrophil recruitment and hypernociception depend on leukotriene B(4) in a murine model of gout. Arthritis Rheum. 2012;64(2):474–84.PubMed

Popa-Nita O, Rollet-Labelle E, Thibault N, Gilbert C, Bourgoin SG, Naccache PH. Crystal-induced neutrophil activation. IX. Syk-dependent activation of class Ia phosphatidylinositol 3-kinase. J Leukoc Biol. 2007;82(3):763–7.PubMed

Martin WJ, Harper JL. Innate inflammation and resolution in acute gout. Immunol Cell Biol. 2010;88(1):15–9.PubMed

Galvao I, Vago JP, Barroso LC, Tavares LP, Queiroz-Junior CM, Costa VV, Carneiro FS, Ferreira TP, Silva PM, Amaral FA, Sousa LP, Teixeira MM. Annexin A1 promotes timely resolution of inflammation in murine gout. Eur J Immunol. 2017;47(3):585–96.PubMed

FitzGerald JD, Dalbeth N, Mikuls T, Brignardello-Petersen R, Guyatt G, Abeles AM, Gelber AC, Harrold LR, Khanna D, King C, Levy G, Libbey C, Mount D, Pillinger MH, Rosenthal A, Singh JA, Sims JE, Smith BJ, Wenger NS, Bae SS, Danve A, Khanna PP, Kim SC, Lenert A, Poon S, Qasim A, Sehra ST, Sharma TSK, Toprover M, Turgunbaev M, Zeng L, Zhang MA, Turner AS, Neogi T. 2020 American College of Rheumatology Guideline for the Management of Gout. Arthritis Care Res (Hoboken). 2020;72(6):744–60.PubMed

10.

Schmitz J, Owyang A, Oldham E, Song Y, Murphy E, McClanahan TK, Zurawski G, Moshrefi M, Qin J, Li X, Gorman DM, Bazan JF, Kastelein RA. IL-33, an interleukin-1-like cytokine that signals via the IL-1 receptor-related protein ST2 and induces T helper type 2-associated cytokines. Immunity. 2005;23(5):479–90.PubMed

11.

Fattori V, Hohmann MSN, Rossaneis AC, Manchope MF, Alves-Filho JC, Cunha TM, Cunha FQ, VerriJr WA. Targeting IL-33/ST2 signaling: regulation of immune function and analgesia. Expert Opin Ther Targets. 2017;21(12):1141–52.PubMed

12.

Martin NT, Martin MU. Interleukin 33 is a guardian of barriers and a local alarmin. Nat Immunol. 2016;17(2):122–31.PubMed

13.

Arshad MI, Piquet-Pellorce C, Samson M. IL-33 and HMGB1 alarmins: sensors of cellular death and their involvement in liver pathology. Liver Int. 2012;32(8):1200–10.PubMed

14.

Fattori V, Borghi SM, Verri WA. IL-33/ST2 signaling boosts inflammation and pain. Proc Natl Acad Sci U S A. 2017;114(47):E10034–5.PubMedPubMedCentral

15.

Verri WA Jr, Souto FO, Vieira SM, Almeida SC, Fukada SY, Xu D, Alves-Filho JC, Cunha TM, Guerrero AT, Mattos-Guimaraes RB, Oliveira FR, Teixeira MM, Silva JS, McInnes IB, Ferreira SH, Louzada-Junior P, Liew FY, Cunha FQ. IL-33 induces neutrophil migration in rheumatoid arthritis and is a target of anti-TNF therapy. Ann Rheum Dis. 2010;69(9):1697–703.PubMed

16.

Alves-Filho JC, Sonego F, Souto FO, Freitas A, Verri WA Jr, Auxiliadora-Martins M, Basile-Filho A, McKenzie AN, Xu D, Cunha FQ, Liew FY. Interleukin-33 attenuates sepsis by enhancing neutrophil influx to the site of infection. Nat Med. 2010;16(6):708–12.PubMed

17.

Lan F, Yuan B, Liu T, Luo X, Huang P, Liu Y, Dai L, Yin H. Interleukin-33 facilitates neutrophil recruitment and bacterial clearance in S. aureus-caused peritonitis. Mol Immunol. 2016;72:74–80.PubMed

18.

Le HT, Tran VG, Kim W, Kim J, Cho HR, Kwon B. IL-33 priming regulates multiple steps of the neutrophil-mediated anti-Candida albicans response by modulating TLR and dectin-1 signals. J Immunol. 2012;189(1):287–95.PubMed

19.

Theoharides TC, Zhang B, Kempuraj D, Tagen M, Vasiadi M, Angelidou A, Alysandratos KD, Kalogeromitros D, Asadi S, Stavrianeas N, Peterson E, Leeman S, Conti P. IL-33 augments substance P-induced VEGF secretion from human mast cells and is increased in psoriatic skin. Proc Natl Acad Sci USA. 2010;107(9):4448–53.PubMed

20.

Taracanova A, Alevizos M, Karagkouni A, Weng Z, Norwitz E, Conti P, Leeman SE, Theoharides TC. SP and IL-33 together markedly enhance TNF synthesis and secretion from human mast cells mediated by the interaction of their receptors. Proc Natl Acad Sci USA. 2017;114(20):E4002–E40094009.PubMed

21.

Xu D, Jiang HR, Kewin P, Li Y, Mu R, Fraser AR, Pitman N, Kurowska-Stolarska M, McKenzie AN, McInnes IB, Liew FY. IL-33 exacerbates antigen-induced arthritis by activating mast cells. Proc Natl Acad Sci USA. 2008;105(31):10913–8.PubMed

22.

Verri WA Jr, Guerrero AT, Fukada SY, Valerio DA, Cunha TM, Xu D, Ferreira SH, Liew FY, Cunha FQ. IL-33 mediates antigen-induced cutaneous and articular hypernociception in mice. Proc Natl Acad Sci USA. 2008;105(7):2723–8.PubMed

23.

Zarpelon AC, Cunha TM, Alves-Filho JC, Pinto LG, Ferreira SH, McInnes IB, Xu D, Liew FY, Cunha FQ, VerriJr WA. IL-33/ST2 signalling contributes to carrageenin-induced innate inflammation and inflammatory pain: role of cytokines, endothelin-1 and prostaglandin E2. Br J Pharmacol. 2013;169(1):90–101.PubMedPubMedCentral

24.

Magro DA, Hohmann MS, Mizokami SS, Cunha TM, Alves-Filho JC, Casagrande R, Ferreira SH, Liew FY, Cunha FQ, VerriJr WA. An interleukin-33/ST2 signaling deficiency reduces overt pain-like behaviors in mice. Braz J Med Biol Res. 2013;46(7):601–6.PubMedPubMedCentral

25.

Zhao J, Zhang H, Liu SB, Han P, Hu S, Li Q, Wang ZF, Mao-Ying QL, Chen HM, Jiang JW, Wu GC, Mi WL, Wang YQ. Spinal interleukin-33 and its receptor ST2 contribute to bone cancer-induced pain in mice. Neuroscience. 2013;253:172–82.PubMed

26.

Liu S, Mi WL, Li Q, Zhang MT, Han P, Hu S, Mao-Ying QL, Wang YQ. Spinal IL-33/ST2 signaling contributes to neuropathic pain via neuronal CaMKII-CREB and astroglial JAK2-STAT3 cascades in mice. Anesthesiology. 2015;123(5):1154–69.PubMed

27.

Han P, Zhao J, Liu SB, Yang CJ, Wang YQ, Wu GC, Xu DM, Mi WL. Interleukin-33 mediates formalin-induced inflammatory pain in mice. Neuroscience. 2013;241:59–66.PubMed

28.

Han P, Liu S, Zhang M, Zhao J, Wang Y, Wu G, Mi W. Inhibition of spinal interlukin-33/ST2 signaling and downstream ERK and JNK pathways in electroacupuncture analgesia in formalin mice. PLoS One. 2015;10(6):e0129576.PubMedPubMedCentral

29.

Ruiz-Miyazawa KW, Staurengo-Ferrari L, Mizokami SS, Domiciano TP, Vicentini F, Camilios-Neto D, Pavanelli WR, Pinge-Filho P, Amaral FA, Teixeira MM, Casagrande R, Verri WA Jr. Quercetin inhibits gout arthritis in mice: induction of an opioid-dependent regulation of inflammasome. Inflammopharmacology. 2017;25:555–70.

30.

Guerrero AT, Verri WA Jr, Cunha TM, Silva TA, Rocha FA, Ferreira SH, Cunha FQ, Parada CA. Hypernociception elicited by tibio-tarsal joint flexion in mice: a novel experimental arthritis model for pharmacological screening. Pharmacol Biochem Behav. 2006;84(2):244–51.PubMed

31.

Fattori V, Rasquel-Oliveira FS, Artero NA, Ferraz CR, Borghi SM, Casagrande R, VerriJr WA. Diosmin treats lipopolysaccharide-induced inflammatory pain and peritonitis by blocking NF-kappaB activation in mice. J Nat Prod. 2020;83(4):1018–26.PubMed

32.

Fattori V, Pinho-Ribeiro FA, Staurengo-Ferrari L, Borghi SM, Rossaneis AC, Casagrande R, Verri WA Jr. The specialized pro-resolving lipid mediator Maresin-1 reduces inflammatory pain with a long-lasting analgesic effect. Br J Pharmacol. 2019;176(11):1728–44.PubMedPubMedCentral

33.

Pichery M, Mirey E, Mercier P, Lefrancais E, Dujardin A, Ortega N, Girard JP. Endogenous IL-33 is highly expressed in mouse epithelial barrier tissues, lymphoid organs, brain, embryos, and inflamed tissues: in situ analysis using a novel Il-33-LacZ gene trap reporter strain. J Immunol. 2012;188(7):3488–95.PubMed

34.

Moussion C, Ortega N, Girard JP. The IL-1-like cytokine IL-33 is constitutively expressed in the nucleus of endothelial cells and epithelial cells in vivo: a novel 'alarmin'? PLoS One. 2008;3(10):e3331.PubMedPubMedCentral

35.

Liew FY, Pitman NI, McInnes IB. Disease-associated functions of IL-33: the new kid in the IL-1 family. Nat Rev Immunol. 2010;10(2):103–10.PubMed

36.

Staurengo-Ferrari L, Trevelin SC, Fattori V, Nascimento DC, de Lima KA, Pelayo JS, Figueiredo F, Casagrande R, Fukada SY, Teixeira MM, Cunha TM, Liew FY, Oliveira RD, Louzada-Junior P, Cunha FQ, Alves-Filho JC, Verri WA. Interleukin-33 receptor (ST2) Deficiency Improves the Outcome of Staphylococcus aureus-induced septic arthritis. Front Immunol. 2018;9:962.PubMedPubMedCentral

37.

Matsuyama Y, Okazaki H, Tamemoto H, Kimura H, Kamata Y, Nagatani K, Nagashima T, Hayakawa M, Iwamoto M, Yoshio T, Tominaga S, Minota S. Increased levels of interleukin 33 in sera and synovial fluid from patients with active rheumatoid arthritis. J Rheumatol. 2010;37(1):18–25.PubMed

38.

Hodzic Z, Schill EM, Bolock AM, Good M. IL-33 and the intestine: the good, the bad, and the inflammatory. Cytokines. 2017;100:1–10.

39.

Kochiashvili G, Kochiashvili D. Urinary IL-33 and galectin-3 increase in patients with interstitial cystitis/bladder pain syndrome (review). Georgian Med News. 2014;232–233:12–5.

40.

Shang K, Wei Y, Su Q, Yu B, Tao Y, He Y, Wang Y, Shi G, Duan L. IL-33 ameliorates the development of MSU-induced inflammation through expanding MDSCs-like cells. Front Endocrinol (Lausanne). 2019;10:36.

41.

Phelps, P.; McCarty, D. J., Jr., Crystal-induced inflammation in canine joints. II. Importance of polymorphonuclear leukocytes. J Exp Med1966, 124, (1), 115–26.

42.

Chang YH, Garalla EJ. Suppression of urate crystal-induced canine joint inflammation by heterologous anti-polymorphonuclear leukocyte serum. Arthritis Rheum. 1968;11(2):145–50.PubMed

43.

Mitroulis I, Kambas K, Ritis K. Neutrophils, IL-1beta, and gout: is there a link? Semin Immunopathol. 2013;35(4):501–12.PubMed

44.

Fattori V, Zarpelon AC, Staurengo-Ferrari L, Borghi SM, Zaninelli TH, Da Costa FB, Alves-Filho JC, Cunha TM, Cunha FQ, Casagrande R, Arakawa NS, Verri WA Jr. Budlein A, a sesquiterpene lactone from viguiera robusta, alleviates pain and inflammation in a model of acute gout arthritis in mice. Front Pharmacol. 2018;9:1076.PubMedPubMedCentral

45.

Mitroulis I, Kambas K, Chrysanthopoulou A, Skendros P, Apostolidou E, Kourtzelis I, Drosos GI, Boumpas DT, Ritis K. Neutrophil extracellular trap formation is associated with IL-1beta and autophagy-related signaling in gout. PLoS One. 2011;6(12):e29318.PubMedPubMedCentral

46.

Amaral FA, Bastos LF, Oliveira TH, Dias AC, Oliveira VL, Tavares LD, Costa VV, Galvao I, Soriani FM, Szymkowski DE, Ryffel B, Souza DG, Teixeira MM. Transmembrane TNF-alpha is sufficient for articular inflammation and hypernociception in a mouse model of gout. Eur J Immunol. 2016;46(1):204–11.PubMed

47.

Cunha TM, Verri WA Jr, Schivo IR, Napimoga MH, Parada CA, Poole S, Teixeira MM, Ferreira SH, Cunha FQ. Crucial role of neutrophils in the development of mechanical inflammatory hypernociception. J Leukoc Biol. 2008;83(4):824–32.PubMed

48.

Fuchs TA, Abed U, Goosmann C, Hurwitz R, Schulze I, Wahn V, Weinrauch Y, Brinkmann V, Zychlinsky A. Novel cell death program leads to neutrophil extracellular traps. J Cell Biol. 2007;176(2):231–41.PubMedPubMedCentral

49.

Carreira EU, Carregaro V, Teixeira MM, Moriconi A, Aramini A, Verri WA Jr, Ferreira SH, Cunha FQ, Cunha TM. Neutrophils recruited by CXCR1/2 signalling mediate post-incisional pain. Eur J Pain. 2013;17(5):654–63.PubMed

50.

Hattori H, Subramanian KK, Sakai J, Jia Y, Li Y, Porter TF, Loison F, Sarraj B, Kasorn A, Jo H, Blanchard C, Zirkle D, McDonald D, Pai SY, Serhan CN, Luo HR. Small-molecule screen identifies reactive oxygen species as key regulators of neutrophil chemotaxis. Proc Natl Acad Sci USA. 2010;107(8):3546–51.PubMed

51.

Zarpelon AC, Rodrigues FC, Lopes AH, Souza GR, Carvalho TT, Pinto LG, Xu D, Ferreira SH, Alves-Filho JC, McInnes IB, Ryffel B, Quesniaux VF, Reverchon F, Mortaud S, Menuet A, Liew FY, Cunha FQ, Cunha TM, VerriJr WA. Spinal cord oligodendrocyte-derived alarmin IL-33 mediates neuropathic pain. FASEB J. 2016;30(1):54–655.PubMed

52.

Huang SJ, Yan JQ, Luo H, Zhou LY, Luo JG. IL-33/ST2 signaling contributes to radicular pain by modulating MAPK and NF-kappaB activation and inflammatory mediator expression in the spinal cord in rat models of noncompressive lumber disk herniation. J Neuroinflamm. 2018;15(1):12.

53.

Liu B, Tai Y, Achanta S, Kaelberer MM, Caceres AI, Shao X, Fang J, Jordt SE. IL-33/ST2 signaling excites sensory neurons and mediates itch response in a mouse model of poison ivy contact allergy. Proc Natl Acad Sci USA. 2016;113(47):E7572–E75797579.PubMed

54.

Chiu IM, Barrett LB, Williams EK, Strochlic DE, Lee S, Weyer AD, Lou S, Bryman GS, Roberson DP, Ghasemlou N, Piccoli C, Ahat E, Wang V, Cobos EJ, Stucky CL, Ma Q, Liberles SD, Woolf CJ. Transcriptional profiling at whole population and single cell levels reveals somatosensory neuron molecular diversity. Elife. 2014;19(3):e04660.

Titel: IL-33 enhances macrophage release of IL-1β and promotes pain and inflammation in gouty arthritis
verfasst von: Victor Fattori
Larissa Staurengo-Ferrari
Tiago H. Zaninelli
Rubia Casagrande
Rene D. Oliveira
Paulo Louzada-Junior
Thiago M. Cunha
Jose C. Alves-Filho
Mauro M. Teixeira
Fernando Q. Cunha
Flavio A. Amaral
Waldiceu A. Verri Jr
Publikationsdatum: 04.09.2020
Verlag: Springer International Publishing
Erschienen in: Inflammation Research / Ausgabe 12/2020
Print ISSN: 1023-3830
Elektronische ISSN: 1420-908X
DOI: https://doi.org/10.1007/s00011-020-01399-x

Leitlinien kompakt für die Innere Medizin

Mit medbee Pocketcards sicher entscheiden.

^{Seit 2022 gehört die medbee GmbH zum Springer Medizin Verlag}

Kostenlos registrieren

Neu im Fachgebiet Innere Medizin

Notfall-TEP der Hüfte ist auch bei 90-Jährigen machbar

26.04.2024 Hüft-TEP Nachrichten

Ob bei einer Notfalloperation nach Schenkelhalsfraktur eine Hemiarthroplastik oder eine totale Endoprothese (TEP) eingebaut wird, sollte nicht allein vom Alter der Patientinnen und Patienten abhängen. Auch über 90-Jährige können von der TEP profitieren.

Niedriger diastolischer Blutdruck erhöht Risiko für schwere kardiovaskuläre Komplikationen

25.04.2024 Hypotonie Nachrichten

Wenn unter einer medikamentösen Hochdrucktherapie der diastolische Blutdruck in den Keller geht, steigt das Risiko für schwere kardiovaskuläre Ereignisse: Darauf deutet eine Sekundäranalyse der SPRINT-Studie hin.

Bei schweren Reaktionen auf Insektenstiche empfiehlt sich eine spezifische Immuntherapie

25.04.2024 Allergien und Intoleranzreaktionen Nachrichten

Insektenstiche sind bei Erwachsenen die häufigsten Auslöser einer Anaphylaxie. Einen wirksamen Schutz vor schweren anaphylaktischen Reaktionen bietet die allergenspezifische Immuntherapie. Jedoch kommt sie noch viel zu selten zum Einsatz.

Therapiestart mit Blutdrucksenkern erhöht Frakturrisiko

25.04.2024 Hypertonie Nachrichten

Beginnen ältere Männer im Pflegeheim eine Antihypertensiva-Therapie, dann ist die Frakturrate in den folgenden 30 Tagen mehr als verdoppelt. Besonders häufig stürzen Demenzkranke und Männer, die erstmals Blutdrucksenker nehmen. Dafür spricht eine Analyse unter US-Veteranen.

Update Innere Medizin

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

Newsletter bestellen

Springer Medizin

Abstract

Objective

Material

Methods

Results

Conclusion

Bitte loggen Sie sich ein, um Zugang zu diesem Inhalt zu erhalten

Weitere Artikel der Ausgabe 12/2020

Don't worry! The next generation would be more resistant to SARS-CoV-2

Cellular and molecular events of inflammation induced transdifferentiation (EMT) and regeneration (MET) in mesenteric mesothelial cells

Roflumilast prevents lymphotoxin α (TNF-β)-induced inflammation activation and degradation of type 2 collagen in chondrocytes

Methyl gallate attenuates inflammation induced by Toll-like receptor ligands by inhibiting MAPK and NF-Κb signaling pathways

Biochanin A attenuates zymosan-induced arthritis in mice similarly to 17-β estradiol: an alternative to hormone replacement therapy?