Home LiteratureArticle Details
PMID: 18827826 Published · ppublish English Journal Article Review

The IL-33/ST2 pathway: therapeutic target and novel biomarker.

Nature reviews. Drug discovery ·Vol. 7 ·No. 10 ·2008-10-00 ·Pages 827-40

Kakkar R, Lee RT

Abstract

For many years, the interleukin-1 receptor family member ST2 was an orphan receptor that was studied in the context of inflammatory and autoimmune disease. However, in 2005, a new cytokine--interleukin-33 (IL-33)--was identified as a functional ligand for ST2. IL-33/ST2 signalling is involved in T-cell mediated immune responses, but more recently, an unanticipated role in cardiovascular disease has been demonstrated. IL-33/ST2 not only represents a promising cardiovascular biomarker but also a novel mechanism of intramyocardial fibroblast-cardiomyocyte communication that may prove to be a therapeutic target for the prevention of heart failure.

MeSH Terms
Animals Atherosclerosis/etiology,metabolism Biomarkers/metabolism Disease Progression Drug Delivery Systems/methods,trends Humans Interleukin-1 Receptor-Like 1 Protein Interleukin-33 Interleukins/agonists,antagonists & inhibitors,metabolism,physiology Receptors, Cell Surface/agonists,antagonists & inhibitors,metabolism,physiology Signal Transduction/drug effects,physiology
Chemicals
Biomarkers IL1RL1 protein, human IL33 protein, human Interleukin-1 Receptor-Like 1 Protein Interleukin-33 Interleukins Receptors, Cell Surface
Authors & Affiliations
2 authors, click to expand affiliations / ORCID
Kakkar Rahul
GRB-804, Division of Cardiology, Massachusetts General Hospital, Boston, Massachussetts 02114, USA. [email protected]
Lee Richard T
References (171)
171 references, click to expand
  1. Beyond cholesterol. Modifications of low-density lipoprotein that increase its atherogenicity.
    N Engl J Med. 1989 Apr 6;320(14):915-24 PMID: 2648148
  2. T and B lymphocytes play a minor role in atherosclerotic plaque formation in the apolipoprotein E-deficient mouse.
    Proc Natl Acad Sci U S A. 1997 Apr 29;94(9):4642-6 PMID: 9114044
  3. IL-1 and IL-18 receptors, and their extended family.
    Curr Opin Immunol. 2002 Feb;14(1):117-22 PMID: 11790541
  4. Regional accumulations of T cells, macrophages, and smooth muscle cells in the human atherosclerotic plaque.
    Arteriosclerosis. 1986 Mar-Apr;6(2):131-8 PMID: 2937395
  5. The immune response in atherosclerosis: a double-edged sword.
    Nat Rev Immunol. 2006 Jul;6(7):508-19 PMID: 16778830
  6. IL-5 links adaptive and natural immunity specific for epitopes of oxidized LDL and protects from atherosclerosis.
    J Clin Invest. 2004 Aug;114(3):427-37 PMID: 15286809
  7. The IL-1 receptor accessory protein (AcP) is required for IL-33 signaling and soluble AcP enhances the ability of soluble ST2 to inhibit IL-33.
    Cytokine. 2008 Jun;42(3):358-64 PMID: 18450470
  8. Cardiovascular events associated with rofecoxib in a colorectal adenoma chemoprevention trial.
    N Engl J Med. 2005 Mar 17;352(11):1092-102 PMID: 15713943
  9. Myocardial infarct-sparing effect of adenosine A2A receptor activation is due to its action on CD4+ T lymphocytes.
    Circulation. 2006 Nov 7;114(19):2056-64 PMID: 17060376
  10. Interleukin-1 receptor cluster: gene organization of IL1R2, IL1R1, IL1RL2 (IL-1Rrp2), IL1RL1 (T1/ST2), and IL18R1 (IL-1Rrp) on human chromosome 2q.
    Genomics. 1999 Apr 1;57(1):177-9 PMID: 10191101
  11. Detection of activated T lymphocytes in the human atherosclerotic plaque.
    Am J Pathol. 1989 Jul;135(1):169-75 PMID: 2505620
  12. Interleukin-4 deficiency decreases atherosclerotic lesion formation in a site-specific manner in female LDL receptor-/- mice.
    Arterioscler Thromb Vasc Biol. 2002 Mar 1;22(3):456-61 PMID: 11884290
  13. Molecular cloning of the chicken ST2 gene and a novel variant form of the ST2 gene product, ST2LV.
    Biochim Biophys Acta. 2004 Nov 24;1681(1):1-14 PMID: 15566939
  14. IL-1 receptor accessory protein is essential for IL-33-induced activation of T lymphocytes and mast cells.
    Proc Natl Acad Sci U S A. 2007 Nov 20;104(47):18660-5 PMID: 18003919
  15. ST2 protein induced by inflammatory stimuli can modulate acute lung inflammation.
    Biochem Biophys Res Commun. 2002 Nov 22;299(1):18-24 PMID: 12435383
  16. Structural basis for signal transduction by the Toll/interleukin-1 receptor domains.
    Nature. 2000 Nov 2;408(6808):111-5 PMID: 11081518
  17. Pathological hypertrophy and cardiac interstitium. Fibrosis and renin-angiotensin-aldosterone system.
    Circulation. 1991 Jun;83(6):1849-65 PMID: 1828192
  18. Th2-predominant inflammation and blockade of IFN-gamma signaling induce aneurysms in allografted aortas.
    J Clin Invest. 2004 Jul;114(2):300-8 PMID: 15254597
  19. The effect of cortisone on experimentally produced myocardial infarcts.
    Circulation. 1955 May;11(5):742-8 PMID: 14364748
  20. Natriuretic peptides.
    J Am Coll Cardiol. 2007 Dec 18;50(25):2357-68 PMID: 18154959
  21. TLR signaling: an emerging bridge from innate immunity to atherogenesis.
    J Immunol. 2004 Nov 15;173(10):5901-7 PMID: 15528321
  22. Presence of a novel primary response gene ST2L, encoding a product highly similar to the interleukin 1 receptor type 1.
    FEBS Lett. 1993 Feb 22;318(1):83-7 PMID: 7916701
  23. IFN-gamma potentiates atherosclerosis in ApoE knock-out mice.
    J Clin Invest. 1997 Jun 1;99(11):2752-61 PMID: 9169506
  24. Expression of IL-4 and IL-5 mRNA and protein product by CD4+ and CD8+ T cells, eosinophils, and mast cells in bronchial biopsies obtained from atopic and nonatopic (intrinsic) asthmatics.
    J Immunol. 1997 Apr 1;158(7):3539-44 PMID: 9120316
  25. T cells in atherogenesis: for better or for worse?
    Arterioscler Thromb Vasc Biol. 2006 Nov;26(11):2421-32 PMID: 16973967
  26. Identification of two distinct subpopulations of Leishmania major-specific T helper 2 cells.
    Infect Immun. 2002 Oct;70(10):5512-20 PMID: 12228277
  27. IL-1 receptor accessory protein and ST2 comprise the IL-33 receptor complex.
    J Immunol. 2007 Aug 15;179(4):2551-5 PMID: 17675517
  28. Spontaneous hypercholesterolemia and arterial lesions in mice lacking apolipoprotein E.
    Science. 1992 Oct 16;258(5081):468-71 PMID: 1411543
  29. An IL-1 family member requires caspase-1 processing and signals through the ST2 receptor.
    Immunity. 2005 Nov;23(5):461-2 PMID: 16286013
  30. Identification of human ST2 protein in the sera of patients with autoimmune diseases.
    Biochem Biophys Res Commun. 2001 Jun 29;284(5):1104-8 PMID: 11414697
  31. Role of cell type-specific promoters in the developmental regulation of T1, an interleukin 1 receptor homologue.
    Cell Growth Differ. 1995 Feb;6(2):179-84 PMID: 7756176
  32. Molecular characterization of NF-HEV, a nuclear factor preferentially expressed in human high endothelial venules.
    Am J Pathol. 2003 Jul;163(1):69-79 PMID: 12819012
  33. Severe hypercholesterolemia and atherosclerosis in apolipoprotein E-deficient mice created by homologous recombination in ES cells.
    Cell. 1992 Oct 16;71(2):343-53 PMID: 1423598
  34. The histopathologic evolution of myocardial infarction.
    Chest. 1978 Jun;73(6):843-9 PMID: 657859
  35. The N-terminal Pro-BNP investigation of dyspnea in the emergency department (PRIDE) study.
    Am J Cardiol. 2005 Apr 15;95(8):948-54 PMID: 15820160
  36. Common and unique mechanisms regulate fibrosis in various fibroproliferative diseases.
    J Clin Invest. 2007 Mar;117(3):524-9 PMID: 17332879
  37. Generation of mice carrying a mutant apolipoprotein E gene inactivated by gene targeting in embryonic stem cells.
    Proc Natl Acad Sci U S A. 1992 May 15;89(10):4471-5 PMID: 1584779
  38. Selective expression of a stable cell surface molecule on type 2 but not type 1 helper T cells.
    J Exp Med. 1998 Mar 2;187(5):787-94 PMID: 9480988
  39. T helper subset development: roles of instruction, selection, and transcription.
    J Clin Invest. 2002 Feb;109(4):431-5 PMID: 11854312
  40. The increase in serum soluble ST2 protein upon acute exacerbation of idiopathic pulmonary fibrosis.
    Chest. 2003 Oct;124(4):1206-14 PMID: 14555548
  41. Deleterious effects of methylprednisolone in patients with myocardial infarction.
    Circulation. 1976 Mar;53(3 Suppl):I204-6 PMID: 1253361
  42. The "T" in trauma: the helper T-cell response and the role of immunomodulation in trauma and burn patients.
    J Trauma. 2007 Dec;63(6):1407-17 PMID: 18212667
  43. Toward transcriptional therapies for the failing heart: chemical screens to modulate genes.
    J Clin Invest. 2005 Mar;115(3):538-46 PMID: 15765135
  44. A novel IL-1 family cytokine, IL-33, potently activates human eosinophils.
    J Allergy Clin Immunol. 2008 Jun;121(6):1484-90 PMID: 18539196
  45. Presence and expression of a novel variant form of ST2 gene product in human leukemic cell line UT-7/GM.
    Biochem Biophys Res Commun. 1999 Oct 14;264(1):14-8 PMID: 10527832
  46. Failure to reduce the size of experimentally produced myocardial infarcts by cortisone treatment.
    Circulation. 1953 Oct;8(4):544-8 PMID: 13094791
  47. Shift toward T lymphocytes with a T helper 1 cytokine-secretion profile in the joints of patients with rheumatoid arthritis.
    Arthritis Rheum. 1996 Dec;39(12):1961-9 PMID: 8961900
  48. Administration of IL-33 induces airway hyperresponsiveness and goblet cell hyperplasia in the lungs in the absence of adaptive immune system.
    Int Immunol. 2008 Jun;20(6):791-800 PMID: 18448455
  49. IL-33 amplifies both Th1- and Th2-type responses through its activity on human basophils, allergen-reactive Th2 cells, iNKT and NK cells.
    Int Immunol. 2008 Aug;20(8):1019-30 PMID: 18550585
  50. Soluble ST2 blocks interleukin-33 signaling in allergic airway inflammation.
    J Biol Chem. 2007 Sep 7;282(36):26369-80 PMID: 17623648
  51. IL-33: a sheep in wolf's clothing?
    Sci STKE. 2007 Jun 12;2007(390):pe31 PMID: 17565120
  52. Cardiac plasticity.
    N Engl J Med. 2008 Mar 27;358(13):1370-80 PMID: 18367740
  53. The TIMI risk score for unstable angina/non-ST elevation MI: A method for prognostication and therapeutic decision making.
    JAMA. 2000 Aug 16;284(7):835-42 PMID: 10938172
  54. Identification of serum soluble ST2 receptor as a novel heart failure biomarker.
    Circulation. 2003 Feb 11;107(5):721-6 PMID: 12578875
  55. Complementary roles for biomarkers of biomechanical strain ST2 and N-terminal prohormone B-type natriuretic peptide in patients with ST-elevation myocardial infarction.
    Circulation. 2008 Apr 15;117(15):1936-44 PMID: 18378613
  56. Active caspase-1 is a regulator of unconventional protein secretion.
    Cell. 2008 Mar 7;132(5):818-31 PMID: 18329368
  57. Expression and regulation of ST2, an interleukin-1 receptor family member, in cardiomyocytes and myocardial infarction.
    Circulation. 2002 Dec 3;106(23 ):2961-6 PMID: 12460879
  58. Crucial role of the interleukin 1 receptor family member T1/ST2 in T helper cell type 2-mediated lung mucosal immune responses.
    J Exp Med. 1999 Oct 4;190(7):895-902 PMID: 10510079
  59. Toll-like receptor-4 modulates survival by induction of left ventricular remodeling after myocardial infarction in mice.
    J Immunol. 2008 May 15;180(10):6954-61 PMID: 18453617
  60. A putative protein of a growth specific cDNA from BALB/c-3T3 cells is highly similar to the extracellular portion of mouse interleukin 1 receptor.
    FEBS Lett. 1989 Dec 4;258(2):301-4 PMID: 2532153
  61. A novel pathway regulating lipopolysaccharide-induced shock by ST2/T1 via inhibition of Toll-like receptor 4 expression.
    J Immunol. 2001 Jun 1;166(11):6633-9 PMID: 11359817
  62. Interleukin-18/interleukin-18 binding protein signaling modulates atherosclerotic lesion development and stability.
    Circ Res. 2001 Sep 28;89(7):E41-5 PMID: 11577031
  63. Structure, function and regulation of the Toll/IL-1 receptor adaptor proteins.
    Immunol Cell Biol. 2007 Aug-Sep;85(6):411-9 PMID: 17667936
  64. Transfer of CD4(+) T cells aggravates atherosclerosis in immunodeficient apolipoprotein E knockout mice.
    Circulation. 2000 Dec 12;102(24):2919-22 PMID: 11113040
  65. The role of interleukin-4 and interleukin-12 in the progression of atherosclerosis in apolipoprotein E-deficient mice.
    Am J Pathol. 2003 Sep;163(3):1117-25 PMID: 12937153
  66. Protection against myocardial ischemia/reperfusion injury in TLR4-deficient mice is mediated through a phosphoinositide 3-kinase-dependent mechanism.
    J Immunol. 2007 Jun 1;178(11):7317-24 PMID: 17513782
  67. Mechanisms and models in heart failure: the biomechanical model and beyond.
    Circulation. 2005 May 31;111(21):2837-49 PMID: 15927992
  68. Bone matrix deposition of T1, a homologue of interleukin 1 receptors.
    Cell Growth Differ. 1995 Feb;6(2):171-7 PMID: 7756175
  69. Acute eosinophilic pneumonia with increased soluble ST2 in serum and bronchoalveolar lavage fluid.
    Respir Med. 2001 Jun;95(6):532-3 PMID: 11421513
  70. Atherosclerosis. the road ahead.
    Cell. 2001 Feb 23;104(4):503-16 PMID: 11239408
  71. Expression and function of the ST2 gene in a murine model of allergic airway inflammation.
    Clin Exp Allergy. 2002 Oct;32(10 ):1520-6 PMID: 12372135
  72. The role of interleukin 12 in the development of atherosclerosis in ApoE-deficient mice.
    Arterioscler Thromb Vasc Biol. 1999 Mar;19(3):734-42 PMID: 10073981
  73. 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 Nov;23 (5):479-90 PMID: 16286016
  74. The expanding family of interleukin-1 cytokines and their role in destructive inflammatory disorders.
    Clin Exp Immunol. 2007 Aug;149(2):217-25 PMID: 17590166
  75. Pathogen recognition and innate immunity.
    Cell. 2006 Feb 24;124(4):783-801 PMID: 16497588
  76. Serum levels of the interleukin-1 receptor family member ST2 predict mortality and clinical outcome in acute myocardial infarction.
    Circulation. 2004 May 11;109 (18):2186-90 PMID: 15117853
  77. Rosiglitazone evaluated for cardiovascular outcomes--an interim analysis.
    N Engl J Med. 2007 Jul 5;357(1):28-38 PMID: 17551159
  78. IL-33 mediates antigen-induced cutaneous and articular hypernociception in mice.
    Proc Natl Acad Sci U S A. 2008 Feb 19;105(7):2723-8 PMID: 18250323
  79. ST2 is an inhibitor of interleukin 1 receptor and Toll-like receptor 4 signaling and maintains endotoxin tolerance.
    Nat Immunol. 2004 Apr;5(4):373-9 PMID: 15004556
  80. Exogenous interferon-gamma enhances atherosclerosis in apolipoprotein E-/- mice.
    Am J Pathol. 2000 Dec;157(6):1819-24 PMID: 11106554
  81. Cytokine expression in advanced human atherosclerotic plaques: dominance of pro-inflammatory (Th1) and macrophage-stimulating cytokines.
    Atherosclerosis. 1999 Jul;145(1):33-43 PMID: 10428293
  82. The oxidation hypothesis of atherosclerosis.
    Lancet. 1994 Sep 17;344(8925):793-5 PMID: 7916078
  83. Toll-like receptor 4 mediates maladaptive left ventricular remodeling and impairs cardiac function after myocardial infarction.
    Circ Res. 2008 Feb 1;102(2):257-64 PMID: 18007026
  84. A sequence-based map of the nine genes of the human interleukin-1 cluster.
    Genomics. 2002 May;79(5):718-25 PMID: 11991722
  85. MyD88 and NOS2 are essential for toll-like receptor 4-mediated survival effect in cardiomyocytes.
    Am J Physiol Heart Circ Physiol. 2006 Oct;291(4):H1900-9 PMID: 16648192
  86. Identification of the product of the murine ST2 gene.
    Biochim Biophys Acta. 1993 Aug 18;1178(2):194-200 PMID: 8347678
  87. Expression of ST2 in helper T lymphocytes of malignant pleural effusions.
    Am J Respir Crit Care Med. 2002 Apr 1;165(7):1005-9 PMID: 11934729
  88. IL-33 is a chemoattractant for human Th2 cells.
    Eur J Immunol. 2007 Oct;37(10):2779-86 PMID: 17853410
  89. Influence of interferon-gamma on the extent and phenotype of diet-induced atherosclerosis in the LDLR-deficient mouse.
    Arterioscler Thromb Vasc Biol. 2003 Mar 1;23(3):454-60 PMID: 12615659
  90. Serum- and oncoprotein-mediated induction of a gene with sequence similarity to the gene encoding carcinoembryonic antigen.
    Proc Natl Acad Sci U S A. 1989 Aug;86(15):5708-12 PMID: 2527364
  91. Role of neurohormones in ventricular adaptation and failure.
    Am J Cardiol. 1994 Apr 7;73(10):36C-39C PMID: 8166053
  92. A novel therapy of murine collagen-induced arthritis with soluble T1/ST2.
    J Immunol. 2004 Jul 1;173(1):145-50 PMID: 15210768
  93. T1/ST2 is preferentially expressed on murine Th2 cells, independent of interleukin 4, interleukin 5, and interleukin 10, and important for Th2 effector function.
    Proc Natl Acad Sci U S A. 1998 Jun 9;95(12 ):6930-5 PMID: 9618516
  94. The v-mos and c-Ha-ras oncoproteins exert similar effects on the pattern of protein synthesis.
    Oncogene. 1989 Jun;4(6):799-803 PMID: 2525241
  95. The expression of ST2 gene in helper T cells and the binding of ST2 protein to myeloma-derived RPMI8226 cells.
    J Biochem. 1997 Jan;121(1):95-103 PMID: 9058198
  96. T1/ST2--an IL-1 receptor-like modulator of immune responses.
    Cytokine Growth Factor Rev. 2004 Apr-Jun;15(2-3):87-95 PMID: 15110792
  97. Expression of interleukin-18 in human atherosclerotic plaques and relation to plaque instability.
    Circulation. 2001 Oct 2;104(14):1598-603 PMID: 11581135
  98. Interleukin (IL)-33 induces the release of pro-inflammatory mediators by mast cells.
    Cytokine. 2007 Dec;40(3):216-25 PMID: 18023358
  99. Cross-regulatory roles of interleukin (IL)-12 and IL-10 in atherosclerosis.
    J Clin Invest. 1996 May 1;97(9):2130-8 PMID: 8621803
  100. TRAF6 is a critical signal transducer in IL-33 signaling pathway.
    Cell Signal. 2008 Sep;20(9):1679-86 PMID: 18603409
  101. Expression of ST2, an interleukin-1 receptor homologue, is induced by proinflammatory stimuli.
    Biochem Biophys Res Commun. 1997 Jun 27;235(3):474-8 PMID: 9207179
  102. Disruption of the murine IL-4 gene blocks Th2 cytokine responses.
    Nature. 1993 Mar 18;362(6417):245-8 PMID: 8384701
  103. Lymphocyte populations in atherosclerotic lesions of apoE -/- and LDL receptor -/- mice. Decreasing density with disease progression.
    Arterioscler Thromb Vasc Biol. 1996 Aug;16(8):1013-8 PMID: 8696940
  104. Reduced cardiac hypertrophy in toll-like receptor 4-deficient mice following pressure overload.
    Cardiovasc Res. 2005 Nov 1;68(2):224-34 PMID: 15967420
  105. The interleukin-1 receptor family.
    Vitam Horm. 2006;74:229-54 PMID: 17027517
  106. The cellular and molecular response of cardiac myocytes to mechanical stress.
    Annu Rev Physiol. 1997;59:551-71 PMID: 9074777
  107. Cutting edge: The ST2 ligand IL-33 potently activates and drives maturation of human mast cells.
    J Immunol. 2007 Aug 15;179(4):2051-4 PMID: 17675461
  108. Heart failure.
    N Engl J Med. 2003 May 15;348(20):2007-18 PMID: 12748317
  109. IL-33 and ST2 comprise a critical biomechanically induced and cardioprotective signaling system.
    J Clin Invest. 2007 Jun;117(6):1538-49 PMID: 17492053
  110. Role of mechanical and hormonal factors in cardiac remodeling and the biologic limits of myocardial adaptation.
    Am J Cardiol. 1993 Jan 21;71(3):46A-54A PMID: 8422005
  111. Inflammation, atherosclerosis, and coronary artery disease.
    N Engl J Med. 2005 Apr 21;352(16):1685-95 PMID: 15843671
  112. Secreted and membrane-bound isoforms of T1, an orphan receptor related to IL-1-binding proteins, are differently expressed in vivo.
    Dev Biol. 1995 Mar;168(1):86-97 PMID: 7883081
  113. The absence of interleukin 1 receptor-related T1/ST2 does not affect T helper cell type 2 development and its effector function.
    J Exp Med. 1999 Nov 15;190(10 ):1541-8 PMID: 10562328
  114. TIMI risk score for ST-elevation myocardial infarction: A convenient, bedside, clinical score for risk assessment at presentation: An intravenous nPA for treatment of infarcting myocardium early II trial substudy.
    Circulation. 2000 Oct 24;102(17):2031-7 PMID: 11044416
  115. Polyclonal origin of T lymphocytes in human atherosclerotic plaques.
    Lab Invest. 1991 Dec;65(6):654-60 PMID: 1836515
  116. T1, an immunoglobulin superfamily member, is expressed in H-ras-dependent epithelial tumours of mammary cells.
    Oncogene. 1993 Mar;8(3):609-17 PMID: 8437844
  117. De novo expression of killer immunoglobulin-like receptors and signaling proteins regulates the cytotoxic function of CD4 T cells in acute coronary syndromes.
    Circ Res. 2003 Jul 25;93(2):106-13 PMID: 12816883
  118. Pathogenesis of diverse clinical and pathological phenotypes in hypertrophic cardiomyopathy.
    Lancet. 2000 Jan 1;355(9197):58-60 PMID: 10615904
  119. Different promoter usage and multiple transcription initiation sites of the interleukin-1 receptor-related human ST2 gene in UT-7 and TM12 cells.
    Eur J Biochem. 1999 Sep;264(2):397-406 PMID: 10491084
  120. The IL-1 family member 7b translocates to the nucleus and down-regulates proinflammatory cytokines.
    J Immunol. 2008 Apr 15;180(8):5477-82 PMID: 18390730
  121. Characterization of a secreted glycoprotein of the immunoglobulin superfamily inducible by mitogen and oncogene.
    Eur J Biochem. 1992 Mar 15;204(3):1041-7 PMID: 1532358
  122. Transcription of the interleukin-1 receptor-related T1 gene is initiated at different promoters in mast cells and fibroblasts.
    J Biol Chem. 1996 Jan 5;271(1):124-9 PMID: 8550546
  123. Elevated soluble ST2 protein levels in sera of patients with asthma with an acute exacerbation.
    Am J Respir Crit Care Med. 2001 Jul 15;164(2):277-81 PMID: 11463601
  124. Tissue angiotensin system in cardiovascular medicine. A paradigm shift?
    Circulation. 1994 Jan;89(1):493-8 PMID: 8281685
  125. CD1d-dependent activation of NKT cells aggravates atherosclerosis.
    J Exp Med. 2004 Feb 2;199(3):417-22 PMID: 14744994
  126. Lesion development and response to immunization reveal a complex role for CD4 in atherosclerosis.
    Circ Res. 2005 Mar 4;96(4):427-34 PMID: 15662027
  127. IL-33, the IL-1-like cytokine ligand for ST2 receptor, is a chromatin-associated nuclear factor in vivo.
    Proc Natl Acad Sci U S A. 2007 Jan 2;104(1):282-7 PMID: 17185418
  128. Reduction of experimental myocardial infarct size by corticosteroid administration.
    J Clin Invest. 1973 Mar;52(3):599-607 PMID: 4685084
  129. T-bet deficiency reduces atherosclerosis and alters plaque antigen-specific immune responses.
    Proc Natl Acad Sci U S A. 2005 Feb 1;102(5):1596-601 PMID: 15665085
  130. The inflammatory response in myocardial infarction.
    Cardiovasc Res. 2002 Jan;53(1):31-47 PMID: 11744011
  131. IL-33 reduces the development of atherosclerosis.
    J Exp Med. 2008 Feb 18;205(2):339-46 PMID: 18268038
  132. T cells cloned from human rheumatoid synovial membrane functionally represent the Th1 subset.
    Scand J Immunol. 1992 May;35(5):603-10 PMID: 1349769
  133. Expression of Th2 cytokines and the stable Th2 marker ST2L in the absence of IL-4 during Leishmania major infection.
    Eur J Immunol. 1999 Nov;29(11):3621-8 PMID: 10556817
  134. Measurement of the interleukin family member ST2 in patients with acute dyspnea: results from the PRIDE (Pro-Brain Natriuretic Peptide Investigation of Dyspnea in the Emergency Department) study.
    J Am Coll Cardiol. 2007 Aug 14;50(7):607-13 PMID: 17692745
  135. Regulation of smooth muscle cell growth, function and death in vitro by activated mast cells--a potential mechanism for the weakening and rupture of atherosclerotic plaques.
    Biochem Pharmacol. 2003 Oct 15;66(8):1493-8 PMID: 14555226
  136. Myeloid dendritic cells induce Th2 responses to inhaled antigen, leading to eosinophilic airway inflammation.
    J Clin Invest. 2000 Aug;106(4):551-9 PMID: 10953030
  137. Interleukin-1 and neuronal injury.
    Nat Rev Immunol. 2005 Aug;5(8):629-40 PMID: 16034365
  138. Cardiac hypertrophy: the good, the bad, and the ugly.
    Annu Rev Physiol. 2003;65:45-79 PMID: 12524460
  139. Myocardial reperfusion injury.
    N Engl J Med. 2007 Sep 13;357(11):1121-35 PMID: 17855673
  140. Rofecoxib and cardiovascular adverse events in adjuvant treatment of colorectal cancer.
    N Engl J Med. 2007 Jul 26;357(4):360-9 PMID: 17652651
  141. Attenuated pathogenesis of polymicrobial peritonitis in mice after TLR2 agonist pre-treatment involves ST2 up-regulation.
    Int Immunol. 2005 Aug;17 (8):1035-46 PMID: 16000329
  142. Regulation and function of T1/ST2 expression on CD4+ T cells: induction of type 2 cytokine production by T1/ST2 cross-linking.
    J Immunol. 2001 Mar 1;166(5):3143-50 PMID: 11207266
  143. Induction of a mitogen-responsive gene after expression of the Ha-ras oncogene in NIH 3T3 fibroblasts.
    Mol Cell Biol. 1989 Nov;9(11):5207-14 PMID: 2689874
  144. Wall stress and patterns of hypertrophy in the human left ventricle.
    J Clin Invest. 1975 Jul;56(1):56-64 PMID: 124746
  145. T helper-cell phenotype regulates atherosclerosis in mice under conditions of mild hypercholesterolemia.
    Circulation. 2001 May 29;103(21):2610-6 PMID: 11382732
  146. Effect of cortisone on the size of experimentally produced myocardial infarcts.
    Circulation. 1953 Feb;7(2):224-8 PMID: 13019938
  147. Effect of rosiglitazone on the risk of myocardial infarction and death from cardiovascular causes.
    N Engl J Med. 2007 Jun 14;356(24):2457-71 PMID: 17517853
  148. Low density lipoprotein undergoes oxidative modification in vivo.
    Proc Natl Acad Sci U S A. 1989 Feb;86(4):1372-6 PMID: 2465552
  149. Gene expression in fibroblasts and fibrosis: involvement in cardiac hypertrophy.
    Circ Res. 2002 Dec 13;91(12):1103-13 PMID: 12480810
  150. Monoclonal T-cell proliferation and plaque instability in acute coronary syndromes.
    Circulation. 2000 Jun 27;101(25):2883-8 PMID: 10869258
  151. Addition of clopidogrel to aspirin and fibrinolytic therapy for myocardial infarction with ST-segment elevation.
    N Engl J Med. 2005 Mar 24;352(12):1179-89 PMID: 15758000
  152. Use of multiple biomarkers to improve the prediction of death from cardiovascular causes.
    N Engl J Med. 2008 May 15;358(20):2107-16 PMID: 18480203
  153. Genomic organization of the interleukin-1 locus.
    Genomics. 2002 May;79(5):726-33 PMID: 11991723
  154. Effect of immune deficiency on lipoproteins and atherosclerosis in male apolipoprotein E-deficient mice.
    Arterioscler Thromb Vasc Biol. 2001 Jun;21(6):1011-6 PMID: 11397712
  155. The family of five: TIR-domain-containing adaptors in Toll-like receptor signalling.
    Nat Rev Immunol. 2007 May;7(5):353-64 PMID: 17457343
  156. Cardiac fibroblasts: friend or foe?
    Am J Physiol Heart Circ Physiol. 2006 Sep;291(3):H1015-26 PMID: 16617141
  157. Toll-like receptors: critical proteins linking innate and acquired immunity.
    Nat Immunol. 2001 Aug;2(8):675-80 PMID: 11477402
  158. A novel T cell-regulated mechanism modulating allergen-induced airways hyperreactivity in BALB/c mice independently of IL-4 and IL-5.
    J Immunol. 1998 Aug 1;161(3):1501-9 PMID: 9686617
  159. Characterization of signaling pathways activated by the interleukin 1 (IL-1) receptor homologue T1/ST2. A role for Jun N-terminal kinase in IL-4 induction.
    J Biol Chem. 2002 Dec 20;277(51):49205-11 PMID: 12368275
  160. ST2/T1 protein functionally binds to two secreted proteins from Balb/c 3T3 and human umbilical vein endothelial cells but does not bind interleukin 1.
    J Biol Chem. 1995 Nov 17;270(46):27905-13 PMID: 7499265
  161. Mechanisms of disease: pathologic structural remodeling is more than adaptive hypertrophy in hypertensive heart disease.
    Nat Clin Pract Cardiovasc Med. 2005 Apr;2(4):209-16 PMID: 16265485
  162. Tissue distribution and subcellular localization of a variant form of the human ST2 gene product, ST2V.
    Biochem Biophys Res Commun. 2001 Aug 3;285(5):1377-83 PMID: 11478810
  163. Alternative promoter usage of the Fos-responsive gene Fit-1 generates mRNA isoforms coding for either secreted or membrane-bound proteins related to the IL-1 receptor.
    EMBO J. 1994 Mar 1;13(5):1176-88 PMID: 8131748
  164. Innate immunity and toll-like receptors: clinical implications of basic science research.
    J Pediatr. 2004 Apr;144(4):421-9 PMID: 15069387
  165. T1/ST2-deficient mice demonstrate the importance of T1/ST2 in developing primary T helper cell type 2 responses.
    J Exp Med. 2000 Mar 20;191(6):1069-76 PMID: 10727469
  166. Lymphocytes are important in early atherosclerosis.
    J Clin Invest. 2001 Jul;108(2):251-9 PMID: 11457878
  167. ST2 gene induced by type 2 helper T cell (Th2) and proinflammatory cytokine stimuli may modulate lung injury and fibrosis.
    Exp Lung Res. 2007 Mar;33(2):81-97 PMID: 17454104
  168. Fibrotic disease and the T(H)1/T(H)2 paradigm.
    Nat Rev Immunol. 2004 Aug;4(8):583-94 PMID: 15286725
  169. Recombinant ST2 boosts hepatic Th2 response in vivo.
    J Leukoc Biol. 2007 Jul;82(1):124-32 PMID: 17412915
  170. Crystallographic refinement of interleukin 1 beta at 2.0 A resolution.
    Proc Natl Acad Sci U S A. 1989 Dec;86(24):9667-71 PMID: 2602367
  171. Increased levels of soluble ST2 protein and IgG1 production in patients with sepsis and trauma.
    Intensive Care Med. 2004 Jul;30(7):1468-73 PMID: 14991091
Article Info
Journal
Nature reviews. Drug discovery
Abbr.
Nat Rev Drug Discov
ISSN
1474-1784
DOI
10.1038/nrd2660
Email
[email protected]
Published
2008-10-00
Pages
827-40
Language
English
Region
England
NLM ID
101124171
PMCID
PMC4277436
Subset
IM
Grants
NHLBI NIH HHS · R01 HL092930 · United States
External Links
PubMed source DOI: 10.1038/nrd2660 PMC Full Text View journal details
Analysis Services
Analysis Services

Contact

No. 2 Wenbo Road, Zhangqiu District, Jinan, Shandong

Qilu Normal University · Genelibs Bioinformatics Lab

750 Shunhua Rd, Jinan

2F, Bldg F, University Science Park

Tel: 0531-88819269

WeChat Official Account

Follow our WeChat subscription account for real-time updates and the latest in medical and biological research.


Business Email

E-mail: [email protected]

Copyright © 2026.Genelibs Jinan Honghui Biotechnology Co., Ltd. 鲁ICP备20007159号-2