nach oben

Archives of Virology

Erschienen in:

01.09.2013 | Original Article

MicroRNA-21 and -146b are involved in the pathogenesis of murine viral myocarditis by regulating TH-17 differentiation

verfasst von: Yan Li Liu, WeiFeng Wu, Yimin Xue, Mengsha Gao, Yuluan Yan, Qing Kong, Yu Pang, Fan Yang

Erschienen in: Archives of Virology | Ausgabe 9/2013

Einloggen, um Zugang zu erhalten

Abstract

Viral myocarditis (VMC) is a common cardiovascular disease, and microRNAs (miRNAs) have been postulated to be involved in its pathology. Using microarrays, we observed that miRNA-21 and -146b were upregulated in a murine model of VMC. We also found that miRNA-451 was downregulated. In vivo silencing of miRNA-21 and -146b resulted in less-severe VMC. Overexpression of miRNA-451 did not ameliorate the severity of VMC. Further work revealed that inhibition of miRNA-21 and -146b decreased the expression levels of Th17 and RORγt . Overexpression of miRNA-451 had no effect on IL-17 and RORγt expression. Inhibition of miRNA-21 and -146b might ameliorate myocardium inflammation by mediating downregulation of RORγt expression, indicating that these miRNAs are involved in the pathogenesis of murine VMC.

Gupta S, Markham DW, Drazner MH, Mammen PP (2008) Fulminant myocarditis. Nat Clin Pract Cardiovasc Med 51:693–706CrossRef

Fairweather D, Frisancho-Kiss S, Yusung SA, Barrett MA, Davis SE, Gatewood SJ, Njoku DB, Rose NR (2004) Interferon-γ protects against chronic viral myocarditis by reducing mast cell degranulation, fibrosis, and the profibrotic cytokines transforming growth factor-ß1, interleukin-1ß, and interleukin-4 in the heart. Am J Pathol 165:1883–1894PubMedCrossRef

Fairweather D, Frisancho-Kiss S, Yusung SA, Barrett MA, Davis SE, Steele RA, Gatewood SJ, Rose NR (2005) IL-12 Protects against Coxsackievirus B3-Induced Myocarditis by Increasing IFN-gamma and macrophage and neutrophil populations in the heart. J Immunol 174:261–269PubMed

Korn T, Bettelli E, Oukka M, Kuchroo VK (2009) IL-17 and Th17 Cells. Annu Rev Immunol 27:485–517PubMedCrossRef

Miossec P (2009) IL-17 and Th17 cells in human inflammatory diseases. Microbes Infect 11:625–630PubMedCrossRef

Yuan J, Yu M, Lin QW, Cao AL, Yu X, Dong JH, Wang JP, Zhang JH, Wang M, Guo HP, Liao YH (2010) Neutralization of IL-17 inhibits the production of anti-ANT autoantibodies in CVB3-induced acute viral myocarditis. Int Immunopharmacol 10:272–276PubMedCrossRef

Fan Y, Weifeng W, Yuluan Y, Qing K, Yu P (2011) Huang Yanlan: treatment with a neutralizing anti-murine interleukin-17 antibody after the onset of coxsackie virus b3-induced viral myocarditis reduces myocardium inflammation. Virol J 8(1):17PubMedCrossRef

Yang F, Lin S, Huang YL, Wu WF (2010) Alteration of Th17 cells in mice with coxsackie virus induced myocarditis. Chinese J Cardiol 38:790–793

Ichiyama K et al (2008) Foxp3 inhibits RORgammat-mediated IL-17A mRNA transcription through direct interaction with RORgammat. J Biol Chem 283(25):17003–17008PubMedCrossRef

10.

Llave C, Xie Z, Kasschau KD et al (2002) Cleavage of scarecrow-like mRNA targets directed by a class of Arabidopsis miRNA. J Sci 297(5589):2053–2056CrossRef

11.

Zhou X et al (2008) Selective miRNA disruption in T reg cells leads to uncontrolled autoimmunity. J Exp Med 205:1983–1991PubMedCrossRef

12.

Chong MM, Rasmussen JP, Rudensky AY, Littman DR (2008) The RNAseIII enzyme Drosha is critical in T cells for preventing lethal inflammatory disease. J Exp Med 205:2005–2017PubMedCrossRef

13.

Du C, Liu C, Kang J, Zhao G, Ye Z, Huang S, Li Z, Wu Z, Pie G (2009) MicroRNA miR-326 regulates TH-17 differentiation and is associated with the pathogenesis of multiple sclerosis. Nature immunol 10:1252–1260CrossRef

14.

Evdokimov AG, Pokross ME, Egorov NS et al (2006) Structural basis for the fast maturation of Arthropoda green fluorescent protein. EMBO Rep 7(10):1006–1012PubMedCrossRef

15.

Mikkola H, Woods NB, Sjögren M et al (2000) Lentivirus gene transfer in murine hematopoietic progenitor cells is compromised by a delay in proviral integration and results in transduction mosaicism and heterogeneous gene expression in progeny cells. J Virol 74(24):11911–11918PubMedCrossRef

16.

Veldhoen M, Hocking RJ, Atkins CJ, Locksley RM, Stockinger B (2006) TGF-β in the context of an inflammatory cytokine milieu supports de novo differentiation of IL-17-producing T cells. Immunity 24:179–189PubMedCrossRef

17.

Mangan PR, Harrington LE, O’Quinn DB, Helms WS, Bullard DC, Elson CO, Hatton RD, Wahl SM, Schoeb TR, Weaver CT (2006) Transforming growth factor-β induces development of the TH17 lineage. Nature 441:231–234PubMedCrossRef

18.

Korn T, Bettelli E, Gao W, Awasthi A, Jäger A, Strom TB, Oukka M (2007) Kuchroo VK:IL-21 initiates an alternative pathway to induce proinflammatory TH17 cells. Nature 448:484–487PubMedCrossRef

19.

Yang XO, Pappu BP, Nurieva R, Akimzhanov A, Kang HS, Chung Y, Ma L, Shah B, Panopoulos AD, Schluns KS, Watowich SS, Tian Q, Jetten AM, Dong C (2008) Thelper 17 lineage differentiation is programmed by orphan nuclear receptors RORα and RORγ. Immunity 28:29–39PubMedCrossRef

20.

Yang XO, Panopoulos AD, Nurieva R, Chang SH, Wang D, Watowich SS (2007) Dong C:STAT3 regulates cytokine-mediated generation of inflammatory helper T cells. J Biol Chem 282:9358–9363PubMedCrossRef

21.

Jetten AM (2009) Retinoid-related orphan receptors (RORs): critical roles in development, immunity, circadian rhythm, and cellular metabolism. Nucl Recept Signal 7:e003PubMed

22.

Veldhoen M et al (2006) Signals mediated by transforming growth factor-beta initiate autoimmune encephalomyelitis, but chronic inflammation is needed to sustain disease. Nat Immunol 7(11):1151–1156PubMedCrossRef

23.

Malhotra N, Kang J (2010) SMAD2 is essential for TGF beta mediated Th17 cell generation. J Biol Chem 285(38):29044–29048PubMedCrossRef

24.

Takimoto T et al (2010) Smad2 and Smad3 are redundantly essential for the TGF-beta-mediated regulation of regulatory T plasticity and Th1 development. J Immunol 185(2):842–855PubMedCrossRef

25.

Li QJ et al (2007) miR-181a is an intrinsic modulator of T cell sensitivity and selection. Cell 129:147–161PubMedCrossRef

26.

Sheedy FJ, Palsson-McDermott E, Hennessy EJ, Martin C, O’Leary JJ, Ruan Q et al (2010) Negative regulation of TLR4 via targeting of the proinflammatory tumor suppressor PDCD4 by the microRNA miRNA-21. Nat Immunol 11:141–147PubMedCrossRef

27.

Stagakis E, Bertsias G, Verginis P, Nakou M, Hatziapostolou M, Kritikos H, Iliopoulos D, Boumpas DT (2011) Identification of novel microRNA signatures linked to human lupus disease activity and pathogenesis:miRNA-21 regulates aberrant T cell responses through regulation of PDCD4 expression. Ann Rheum Dis 70(8):1496–1506PubMedCrossRef

28.

Narducci MG, Arcelli D, Picchio MC, Lazzeri C, Pagani E, Sampogna F, Scala E, Fadda P, Cristofoletti C, Facchiano A, Frontani M, Monopoli A, Ferracin M, Negrini M, Lombardo GA, Caprini E, Russo G (2011) MicroRNA profiling reveals that miRNA-21, miR486 and miRNA-214 are upregulated and involved in cell survival in Sézary syndrome. Cell Death Dis 2(4):e151PubMedCrossRef

29.

Lu TX, Hartner J, Lim EJ, Fabry V, Mingler MK, Cole ET, Orkin SH, Aronow BJ, Rothenberg ME (2011) MicroRNA-21 limits in vivo immune response-mediated activation of the IL-12/IFN-gamma pathway, Th1 polarization, and the severity of delayed-type hypersensitivity. J Immunol 187(6):3362–3373PubMedCrossRef

30.

Garchow BG, BartulosEncinas O, Leung YT, Tsao PY, Eisenberg RA, Caricchio R, Obad S, Petri A, Kauppinen S, Kiriakidou M (2011) Silencing of microRNA-21 in vivo ameliorates autoimmune splenomegaly in lupus mice. EMBO Mol Med 3(10):605–615PubMedCrossRef

31.

Van der Fits L, van Kester MS, Qin Y, Out-Luiting JJ, Smit F, Zoutman WH, Willemze R, Tensen CP, Vermeer MH (2011) MicroRNA-21 expression in CD4+ T cells is regulated by STAT3 and is pathologically involved in Sézary syndrome. J Invest Dermatol 131(3):762–768PubMedCrossRef

32.

Nakasa T, Miyaki S, Okubo A et al (2008) Expression of MicmRNA-146 in Rheumatoid Arthritis Synovial Tissue[J]. Arthritis Rheum 58(5):1284–1292PubMedCrossRef

33.

Stanczyk J, Pedrioli DM, Brentano F et al (2008) Altered Expression of MicrRNA in Synovial Fibmblasts and Synovial Tissue in Rheumatoid Arthritis[J]. Arthritis Rheum 58(4):1001–1009PubMedCrossRef

34.

Tang Y, Luo X, Cui H et al (2009) MicmRNA-146a Contributes to Abnormal Activation of the Type I Interferon Pathway in Human Lupus by Targeting the Key Signaling Proteins. Arthritis Rheum 60(4):1065–1075PubMedCrossRef

Titel: MicroRNA-21 and -146b are involved in the pathogenesis of murine viral myocarditis by regulating TH-17 differentiation
verfasst von: Yan Li Liu
WeiFeng Wu
Yimin Xue
Mengsha Gao
Yuluan Yan
Qing Kong
Yu Pang
Fan Yang
Publikationsdatum: 01.09.2013
Verlag: Springer Vienna
Erschienen in: Archives of Virology / Ausgabe 9/2013
Print ISSN: 0304-8608
Elektronische ISSN: 1432-8798
DOI: https://doi.org/10.1007/s00705-013-1695-6

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

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

Weitere Artikel der Ausgabe 9/2013

Complete genome sequence of rabies virus CVS-24 from China

The genome of VP3, a T7-like phage used for the typing of Vibrio cholerae

Efficacy of quantitative RT-PCR for detection of the nucleoprotein gene from different porcine rubulavirus strains

A two-tube multiplex real-time RT-PCR assay for the detection of four hemorrhagic fever viruses: severe fever with thrombocytopenia syndrome virus, Hantaan virus, Seoul virus, and dengue virus

Large-scale codon de-optimisation of the p29 replicase gene by synonymous substitutions causes a loss of infectivity of melon necrotic spot virus