Skip to main content
Hauptrubriken
CME Facharzt-Training Webinare Zeitschriften Bücher e.Medpedia Podcast
Service
Jobbörse Info & Hilfe
Fachgebiete
Anästhesiologie Allgemeinmedizin Arbeitsmedizin Augenheilkunde Chirurgie Dermatologie Gynäkologie und Geburtshilfe HNO Innere Medizin Kardiologie Neurologie Onkologie und Hämatologie Orthopädie und Unfallchirurgie Pädiatrie Pathologie Psychiatrie Radiologie Rechtsmedizin Urologie Zahnmedizin
Themen
Typ-2-Diabetes und Adipositas Klimawandel und Gesundheit Neues aus dem Markt COVID-19 Praxis und Beruf Seltene Erkrankungen GOÄ & EBM Panorama
Sammlungen
Kasuistiken Algorithmen & Infografiken Blickdiagnosen Arthropedia FlapFinder (für Dermatochirurgen) Videos Kongressberichterstattung Medizin für Apothekerinnen und Apotheker Für Ärztinnen und Ärzte in Weiterbildung Für Medizinstudierende

Live-Webinar "Urologie und Sexualmedizin in der Praxis"

Häufige urologisch-sexualmedizinische Themen in der Praxis sind das Thema des MMW-Webinars am 5. Juni von 17.30 bis 19 Uhr. Konkret geht es um die Frage, wann bei Harnwegsinfektionen auf Antibiotika verzichtet werden kann, und um ein Update zur Therapie von Libido- und Potenzstörungen des Mannes. Der dritte Vortrag behandelt sexuell übertragbare Krankheiten. Stellen Sie Ihre Fragen an die Experten und sammeln Sie 2 CME-Punkte. Jetzt gleich anmelden!
Erweiterte Suche
Anmelden
nach oben
Journal of Clinical Immunology
Erschienen in: Journal of Clinical Immunology 2/2010

01.03.2010

Inhibition of IFN Regulatory Factor-1 Down-Regulate Th1 Cell Function in Patients with Acute Coronary Syndrome

verfasst von: Min Guo, Xiaobo Mao, Qingwei Ji, Mingjian Lang, Songnan Li, Yudong Peng, Wei Zhou, Bo Xiong, Qiutang Zeng

Erschienen in: Journal of Clinical Immunology | Ausgabe 2/2010

Einloggen, um Zugang zu erhalten

Abstract

Background

The crucial role of T helper (Th) cells and chronic inflammation in atherosclerosis and coronary artery disease is no longer controversial. Evidence has revealed that Th cell type 1 (Th1) is closely associated with the pathogenesis of acute coronary syndrome (ACS). But the mechanisms involved in the generation of Th1 cells have not been fully elucidated. IFN regulatory factor (IRF)-1 is a pleiotropic transcription factor involved in innate immunity and chronic inflammation disease. The study was undertaken to investigate the potential effect of IRF-1 on the Th1 cell function in patients with ACS in vitro.

Methods

Patients with clinical presentation of chest pain, stable angina, unstable angina, and acute myocardial infarction were enrolled in this study. Circulating CD4+ T cells were enriched and analyzed for mRNA and protein expression of IRF-1. Silencing IRF-1 gene with small interfering RNA in CD4+ T cells from patients with ACS was performed to explore the possible mechanisms involved in ACS.

Results

The results demonstrated that the expression of IRF-1 in CD4+ T cells was significantly increased in patients with ACS and positively correlated with plasma Th1 cytokine profile. Inhibition of IRF-1 in CD4+ T cells from patients with ACS prevented the induction of the frequencies and cytokines expression of Th1 cells. In addition, this study also revealed that IRF-1 modulate Th1 differentiation through establishing IL-12 responsiveness by acting on IL-12 receptor β1.

Conclusion

The present data demonstrate that inhibition of IRF-1 obviously decrease the function of Th1 cells and may be a novel participator in the progress of ACS.
Literatur
1.
Hansson GK. Inflammation, atherosclerosis, and coronary artery disease. N Engl J Med. 2005;352:1685–95.CrossRefPubMed
2.
Robertson AK, Hansson GK. T cells in atherogenesis: for better or for worse? Arterioscler Thromb Vasc Biol. 2006;26:2421–32.CrossRefPubMed
3.
4.
Jonasson L, Holm J, Skalli O, Gabbiani G, Hansson GK. Expression of class ii transplantation antigen on vascular smooth muscle cells in human atherosclerosis. J Clin Invest. 1985;76:125–31.CrossRefPubMed
5.
Roselaar SE, Kakkanathu PX, Daugherty A. Lymphocyte populations in atherosclerotic lesions of apoe−/− and ldl receptor−/− mice. Decreasing density with disease progression. Arterioscler Thromb Vasc Biol. 1996;16:1013–8.PubMed
6.
Methe H, Brunner S, Wiegand D, Nabauer M, Koglin J, Edelman ER. Enhanced t-helper-1 lymphocyte activation patterns in acute coronary syndromes. J Am Coll Cardiol. 2005;45:1939–45.CrossRefPubMed
7.
Frostegard J, Ulfgren AK, Nyberg P, Hedin U, Swedenborg J, Andersson U, et al. Cytokine expression in advanced human atherosclerotic plaques: dominance of pro-inflammatory (th1) and macrophage-stimulating cytokines. Atherosclerosis. 1999;145:33–43.CrossRefPubMed
8.
Laurat E, Poirier B, Tupin E, Caligiuri G, Hansson GK, Bariety J, et al. In vivo downregulation of t helper cell 1 immune responses reduces atherogenesis in apolipoprotein e-knockout mice. Circulation. 2001;104:197–202.PubMed
9.
Fisher M, Folland E. Acute ischemic coronary artery disease and ischemic stroke: similarities and differences. Am J Ther. 2008;15:137–49.CrossRefPubMed
10.
Cheng X, Liao YH, Ge H, Li B, Zhang J, Yuan J, et al. Th1/th2 functional imbalance after acute myocardial infarction: coronary arterial inflammation or myocardial inflammation. J Clin Immunol. 2005;25:246–53.CrossRefPubMed
11.
Ji QW, Guo M, Zheng JS, Mao XB, Peng YD, Li SN, et al. Downregulation of t helper cell type 3 in patients with acute coronary syndrome. Arch Med Res. 2009;40:285–93.CrossRefPubMed
12.
Potteaux S, Esposito B, van Oostrom O, Brun V, Ardouin P, Groux H, et al. Leukocyte-derived interleukin 10 is required for protection against atherosclerosis in low-density lipoprotein receptor knockout mice. Arterioscler Thromb Vasc Biol. 2004;24:1474–8.CrossRefPubMed
13.
Pinderski LJ, Fischbein MP, Subbanagounder G, Fishbein MC, Kubo N, Cheroutre H, et al. Overexpression of interleukin-10 by activated t lymphocytes inhibits atherosclerosis in ldl receptor-deficient mice by altering lymphocyte and macrophage phenotypes. Circ Res. 2002;90:1064–71.CrossRefPubMed
14.
Fernandes JL, Mamoni RL, Orford JL, Garcia C, Selwyn AP, Coelho OR, et al. Increased th1 activity in patients with coronary artery disease. Cytokine. 2004;26:131–7.CrossRefPubMed
15.
Liuzzo G, Kopecky SL, Frye RL, O’Fallon WM, Maseri A, Goronzy JJ, et al. Perturbation of the t-cell repertoire in patients with unstable angina. Circulation. 1999;100:2135–9.PubMed
16.
Branen L, Hovgaard L, Nitulescu M, Bengtsson E, Nilsson J, Jovinge S. Inhibition of tumor necrosis factor-alpha reduces atherosclerosis in apolipoprotein e knockout mice. Arterioscler Thromb Vasc Biol. 2004;24:2137–42.CrossRefPubMed
17.
Sato M, Taniguchi T, Tanaka N. The interferon system and interferon regulatory factor transcription factors – studies from gene knockout mice. Cytokine Growth Factor Rev. 2001;12:133–42.CrossRefPubMed
18.
Matsuyama T, Kimura T, Kitagawa M, Pfeffer K, Kawakami T, Watanabe N, et al. Targeted disruption of irf-1 or irf-2 results in abnormal type i ifn gene induction and aberrant lymphocyte development. Cell. 1993;75:83–97.PubMed
19.
Ogasawara K, Hida S, Azimi N, Tagaya Y, Sato T, Yokochi-Fukuda T, et al. Requirement for irf-1 in the microenvironment supporting development of natural killer cells. Nature. 1998;391:700–3.CrossRefPubMed
20.
Coccia EM, Stellacci E, Valtieri M, Masella B, Feccia T, Marziali G, et al. Ectopic expression of interferon regulatory factor-1 potentiates granulocytic differentiation. Biochem J. 2001;360:285–94.CrossRefPubMed
21.
Tada Y, Ho A, Matsuyama T, Mak TW. Reduced incidence and severity of antigen-induced autoimmune diseases in mice lacking interferon regulatory factor-1. J Exp Med. 1997;185:231–8.CrossRefPubMed
22.
Buch T, Uthoff-Hachenberg C, Waisman A. Protection from autoimmune brain inflammation in mice lacking IFN-regulatory factor-1 is associated with Th2-type cytokines. Int Immunol. 2003;15:855–9.CrossRefPubMed
23.
Sommer F, Faller G, Rollinghoff M, Kirchner T, Mak TW, Lohoff M. Lack of gastritis and of an adaptive immune response in interferon regulatory factor-1-deficient mice infected with helicobacter pylori. Eur J Immunol. 2001;31:396–402.CrossRefPubMed
24.
Nakazawa T, Satoh J, Takahashi K, Sakata Y, Ikehata F, Takizawa Y, et al. Complete suppression of insulitis and diabetes in nod mice lacking interferon regulatory factor-1. J Autoimmun. 2001;17:119–25.CrossRefPubMed
25.
Taki S, Sato T, Ogasawara K, Fukuda T, Sato M, Hida S, et al. Multistage regulation of Th1-type immune responses by the transcription factor IRF-1. Immunity. 1997;6:673–9.CrossRefPubMed
26.
Lohoff M, Ferrick D, Mittrucker HW, Duncan GS, Bischof S, Rollinghoff M, et al. Interferon regulatory factor-1 is required for a T helper 1 immune response in vivo. Immunity. 1997;6:681–9.CrossRefPubMed
27.
Unutmaz D, Vilcek J. IRF1: a deus ex machina in Th1 differentiation. Nat Immunol. 2008;9:9–10.CrossRefPubMed
28.
Falk E. Coronary thrombosis: pathogenesis and clinical manifestations. Am J Cardiol. 1991;68:28B–35.CrossRefPubMed
29.
Harrington LE, Hatton RD, Mangan PR, Turner H, Murphy TL, Murphy KM, et al. Interleukin 17-producing CD4+ effector t cells develop via a lineage distinct from the T helper type 1 and 2 lineages. Nat Immunol. 2005;6:1123–32.CrossRefPubMed
30.
Park H, Li Z, Yang XO, Chang SH, Nurieva R, Wang YH, et al. A distinct lineage of CD4 T cells regulates tissue inflammation by producing interleukin 17. Nat Immunol. 2005;6:1133–41.CrossRefPubMed
31.
Buono C, Come CE, Stavrakis G, Maguire GF, Connelly PW, Lichtman AH. Influence of interferon-gamma on the extent and phenotype of diet-induced atherosclerosis in the LDLR-deficient mouse. Arterioscler Thromb Vasc Biol. 2003;23:454–60.CrossRefPubMed
32.
Gupta S, Pablo AM, Jiang X, Wang N, Tall AR, Schindler C. IFN-gamma potentiates atherosclerosis in apoe knock-out mice. J Clin Invest. 1997;99:2752–61.CrossRefPubMed
33.
Whitman SC, Ravisankar P, Daugherty A. IFN-gamma deficiency exerts gender-specific effects on atherogenesis in apolipoprotein e−/− mice. J Interferon Cytokine Res. 2002;22:661–70.CrossRefPubMed
34.
Whitman SC, Ravisankar P, Elam H, Daugherty A. Exogenous interferon-gamma enhances atherosclerosis in apolipoprotein e−/− mice. Am J Pathol. 2000;157:1819–24.PubMed
35.
Fragale A, Gabriele L, Stellacci E, Borghi P, Perrotti E, Ilari R, et al. IFN regulatory factor-1 negatively regulates cd4+ cd25+ regulatory T cell differentiation by repressing foxp3 expression. J Immunol. 2008;181:1673–82.PubMed
36.
Wessely R, Hengst L, Jaschke B, Wegener F, Richter T, Lupetti R, et al. A central role of interferon regulatory factor-1 for the limitation of neointimal hyperplasia. Hum Mol Genet. 2003;12:177–87.CrossRefPubMed
37.
Holvoet P, Davey PC, De Keyzer D, Doukoure M, Deridder E, Bochaton-Piallat ML, et al. Oxidized low-density lipoprotein correlates positively with toll-like receptor 2 and interferon regulatory factor-1 and inversely with superoxide dismutase-1 expression: studies in hypercholesterolemic swine and thp-1 cells. Arterioscler Thromb Vasc Biol. 2006;26:1558–65.CrossRefPubMed
38.
Tamura T, Ishihara M, Lamphier MS, Tanaka N, Oishi I, Aizawa S, et al. An irf-1-dependent pathway of DNA damage-induced apoptosis in mitogen-activated t lymphocytes. Nature. 1995;376:596–9.CrossRefPubMed
39.
Tanaka N, Ishihara M, Kitagawa M, Harada H, Kimura T, Matsuyama T, et al. Cellular commitment to oncogene-induced transformation or apoptosis is dependent on the transcription factor IRF-1. Cell. 1994;77:829–39.CrossRefPubMed
40.
Romeo G, Fiorucci G, Chiantore MV, Percario ZA, Vannucchi S, Affabris E. IRF-1 as a negative regulator of cell proliferation. J Interferon Cytokine Res. 2002;22:39–47.CrossRefPubMed
41.
Kano S, Sato K, Morishita Y, Vollstedt S, Kim S, Bishop K, et al. The contribution of transcription factor IRF1 to the interferon-gamma-interleukin 12 signaling axis and th1 versus th-17 differentiation of cd4+ T cells. Nat Immunol. 2008;9:34–41.CrossRefPubMed
Metadaten
Titel
Inhibition of IFN Regulatory Factor-1 Down-Regulate Th1 Cell Function in Patients with Acute Coronary Syndrome
verfasst von
Min Guo
Xiaobo Mao
Qingwei Ji
Mingjian Lang
Songnan Li
Yudong Peng
Wei Zhou
Bo Xiong
Qiutang Zeng
Publikationsdatum
01.03.2010
Verlag
Springer US
Erschienen in
Journal of Clinical Immunology / Ausgabe 2/2010
Print ISSN: 0271-9142
Elektronische ISSN: 1573-2592
DOI
https://doi.org/10.1007/s10875-010-9367-8

Weitere Artikel der Ausgabe 2/2010

Journal of Clinical Immunology 2/2010 Zur Ausgabe

OriginalPaper

Natural Hidden Autoantibodies to Tissue Transglutaminase Cross-React with Fibrinogen

OriginalPaper

The IL-17 Family Cytokines in Immunity and Disease

OriginalPaper

CpG-Induced Th1-Type Response in the Downmodulation of Early Development of Allergy and Inhibition of B7 Expression on T Cells of Newborn Mice

OriginalPaper

IL-17 Contributes to the Development of Chronic Rejection in a Murine Heart Transplant Model

OriginalPaper

Distinct Phenotype of Unrestricted Cytotoxic T lymphocytes from Human Immunodeficiency Virus-infected Individuals

OriginalPaper

Th17 Cytokines and the Gut Mucosal Barrier

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

Ist Fasten vor Koronarinterventionen wirklich nötig?

04.06.2024 Interventionelle Verfahren in der Kardiologie Nachrichten

Wenn Eingriffe wie eine Koronarangiografie oder eine Koronarangioplastie anstehen, wird häufig empfohlen, in den Stunden zuvor nüchtern zu bleiben. Ein französisches Forscherteam hat diese Maßnahme hinterfragt.

Typ-2-Diabetes: Ernährungsunsicherheit vervierfacht Risiko für schwere Hypoglykämien

04.06.2024 Typ-2-Diabetes Nachrichten

Wenn ältere Menschen mit Typ-2-Diabetes Schwierigkeiten beim Beschaffen und Zubereiten von Mahlzeiten haben, geht dies mit einem deutlich gesteigerten Risiko für schwere Hypoglykämien einher.

Mehr Brustkrebs, aber weniger andere gynäkologische Tumoren mit Levonorgestrel-IUS

04.06.2024 Levonorgestrel Nachrichten

Unter Frauen, die ein Levonorgestrel-freisetzendes intrauterines System (IUS) verwenden, ist die Brustkrebsrate um 13% erhöht. Dafür kommt es deutlich seltener zu Endometrium-, Zervix- und Ovarialkarzinomen.

GLP-1-Agonist Semaglutid wirkt kardio- und nephroprotektiv

03.06.2024 Semaglutid Nachrichten

Der GLP-1-Agonist Semaglutid hat in der FLOW-Studie bewiesen, dass sich damit die Progression chronischer Nierenerkrankungen bei Patienten mit Typ-2-Diabetes bremsen lässt. Auch in kardiovaskulärer Hinsicht war die Therapie erfolgreich.

Update Innere Medizin

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

Newsletter bestellen
Bildnachweise