Activation of interleukin-1 family receptor ST2L by its ligand interleukin-33 (IL-33) is an important component in inflammatory responses. Peripheral blood basophils, recognized as major effector cells in allergic inflammation that play a role in both innate and adaptive immunity, are activated by IL-33 through ST2L. However, studies are challenging due to the paucity of this cell population, representing less than 1% of peripheral blood leukocytes. We identified a basophil-like chronic myelogenous leukemia cell line, KU812, that constitutively expresses ST2L and demonstrates functional responses to IL-33 stimulation. IL-33 induced production of multiple inflammatory mediators in KU812 cells that were blocked by anti-ST2L and anti-IL-33 antibodies. The interaction of IL-33 and ST2L activated NF-kappa B, JNK, and p38 MAPK, but not ERK1/2 signaling pathways. Studies using pharmacological inhibitors to IKK-2 and MAP kinases revealed that one of the functional responses, IL-33-induced IL-13 production, was regulated through NF-kappa B, but not JNK or p38 MAPK signaling. The requirement of NF-kappa B was confirmed by IKK-2 knockdown using shRNA. KU812 represents the first human cell line-based in vitro model of the IL-33/ST2L axis and provides a valuable tool to aid in understanding the mechanism and significance of IL-33 and ST2L interaction and function. (C) 2010 Elsevier Inc. All rights reserved.
机构:Univ Paris 05, Hop Necker Enfants Malad, CNRS, Fac Med,UMR 8147,urR8147, F-75005 Paris, France
Bourgeois, Elvire
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Van, Linh Pham
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Samson, Michel
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Univ Rennes 1, INSERM, 1FR 140, U620, Rennes, FranceUniv Paris 05, Hop Necker Enfants Malad, CNRS, Fac Med,UMR 8147,urR8147, F-75005 Paris, France
Samson, Michel
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Diem, Severine
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机构:Univ Paris 05, Hop Necker Enfants Malad, CNRS, Fac Med,UMR 8147,urR8147, F-75005 Paris, France
Diem, Severine
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Barra, Anne
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Univ Poitiers, Immunol Lab, Poitiers, France
Ctr Hosp Univ CHU Poitiers, Poitiers, FranceUniv Paris 05, Hop Necker Enfants Malad, CNRS, Fac Med,UMR 8147,urR8147, F-75005 Paris, France
Barra, Anne
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Roga, Stephane
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Univ Toulouse, CNRS, IPBS, UMR5089, Toulouse, FranceUniv Paris 05, Hop Necker Enfants Malad, CNRS, Fac Med,UMR 8147,urR8147, F-75005 Paris, France
Roga, Stephane
;
Gombert, Jean-Marc
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Univ Poitiers, Immunol Lab, Poitiers, France
Ctr Hosp Univ CHU Poitiers, Poitiers, FranceUniv Paris 05, Hop Necker Enfants Malad, CNRS, Fac Med,UMR 8147,urR8147, F-75005 Paris, France
Gombert, Jean-Marc
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Schneider, Elke
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机构:Univ Paris 05, Hop Necker Enfants Malad, CNRS, Fac Med,UMR 8147,urR8147, F-75005 Paris, France
Schneider, Elke
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Dy, Michel
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机构:Univ Paris 05, Hop Necker Enfants Malad, CNRS, Fac Med,UMR 8147,urR8147, F-75005 Paris, France
Dy, Michel
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Gourdy, Pierre
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Fac Med Toulouse, INSERM, U858, F-31073 Toulouse, FranceUniv Paris 05, Hop Necker Enfants Malad, CNRS, Fac Med,UMR 8147,urR8147, F-75005 Paris, France
Gourdy, Pierre
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Girard, Jean-Philippe
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Univ Toulouse, CNRS, IPBS, UMR5089, Toulouse, FranceUniv Paris 05, Hop Necker Enfants Malad, CNRS, Fac Med,UMR 8147,urR8147, F-75005 Paris, France
Girard, Jean-Philippe
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Herbelin, Andre
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Univ Paris 05, Hop Necker Enfants Malad, CNRS, Fac Med,UMR 8147,urR8147, F-75005 Paris, FranceUniv Paris 05, Hop Necker Enfants Malad, CNRS, Fac Med,UMR 8147,urR8147, F-75005 Paris, France
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Univ Sheffield, Royal Hallamshire Hosp, Div Mol & Genet Med, Sheffield S10 2JF, S Yorkshire, EnglandUniv Sheffield, Royal Hallamshire Hosp, Div Mol & Genet Med, Sheffield S10 2JF, S Yorkshire, England
Dale, M
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Nicklin, MJH
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Univ Sheffield, Royal Hallamshire Hosp, Div Mol & Genet Med, Sheffield S10 2JF, S Yorkshire, EnglandUniv Sheffield, Royal Hallamshire Hosp, Div Mol & Genet Med, Sheffield S10 2JF, S Yorkshire, England
机构:Univ Paris 05, Hop Necker Enfants Malad, CNRS, Fac Med,UMR 8147,urR8147, F-75005 Paris, France
Bourgeois, Elvire
;
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机构:
Van, Linh Pham
;
Samson, Michel
论文数: 0引用数: 0
h-index: 0
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Univ Rennes 1, INSERM, 1FR 140, U620, Rennes, FranceUniv Paris 05, Hop Necker Enfants Malad, CNRS, Fac Med,UMR 8147,urR8147, F-75005 Paris, France
Samson, Michel
;
Diem, Severine
论文数: 0引用数: 0
h-index: 0
机构:Univ Paris 05, Hop Necker Enfants Malad, CNRS, Fac Med,UMR 8147,urR8147, F-75005 Paris, France
Diem, Severine
;
Barra, Anne
论文数: 0引用数: 0
h-index: 0
机构:
Univ Poitiers, Immunol Lab, Poitiers, France
Ctr Hosp Univ CHU Poitiers, Poitiers, FranceUniv Paris 05, Hop Necker Enfants Malad, CNRS, Fac Med,UMR 8147,urR8147, F-75005 Paris, France
Barra, Anne
;
Roga, Stephane
论文数: 0引用数: 0
h-index: 0
机构:
Univ Toulouse, CNRS, IPBS, UMR5089, Toulouse, FranceUniv Paris 05, Hop Necker Enfants Malad, CNRS, Fac Med,UMR 8147,urR8147, F-75005 Paris, France
Roga, Stephane
;
Gombert, Jean-Marc
论文数: 0引用数: 0
h-index: 0
机构:
Univ Poitiers, Immunol Lab, Poitiers, France
Ctr Hosp Univ CHU Poitiers, Poitiers, FranceUniv Paris 05, Hop Necker Enfants Malad, CNRS, Fac Med,UMR 8147,urR8147, F-75005 Paris, France
Gombert, Jean-Marc
;
Schneider, Elke
论文数: 0引用数: 0
h-index: 0
机构:Univ Paris 05, Hop Necker Enfants Malad, CNRS, Fac Med,UMR 8147,urR8147, F-75005 Paris, France
Schneider, Elke
;
Dy, Michel
论文数: 0引用数: 0
h-index: 0
机构:Univ Paris 05, Hop Necker Enfants Malad, CNRS, Fac Med,UMR 8147,urR8147, F-75005 Paris, France
Dy, Michel
;
Gourdy, Pierre
论文数: 0引用数: 0
h-index: 0
机构:
Fac Med Toulouse, INSERM, U858, F-31073 Toulouse, FranceUniv Paris 05, Hop Necker Enfants Malad, CNRS, Fac Med,UMR 8147,urR8147, F-75005 Paris, France
Gourdy, Pierre
;
Girard, Jean-Philippe
论文数: 0引用数: 0
h-index: 0
机构:
Univ Toulouse, CNRS, IPBS, UMR5089, Toulouse, FranceUniv Paris 05, Hop Necker Enfants Malad, CNRS, Fac Med,UMR 8147,urR8147, F-75005 Paris, France
Girard, Jean-Philippe
;
Herbelin, Andre
论文数: 0引用数: 0
h-index: 0
机构:
Univ Paris 05, Hop Necker Enfants Malad, CNRS, Fac Med,UMR 8147,urR8147, F-75005 Paris, FranceUniv Paris 05, Hop Necker Enfants Malad, CNRS, Fac Med,UMR 8147,urR8147, F-75005 Paris, France
机构:
Univ Sheffield, Royal Hallamshire Hosp, Div Mol & Genet Med, Sheffield S10 2JF, S Yorkshire, EnglandUniv Sheffield, Royal Hallamshire Hosp, Div Mol & Genet Med, Sheffield S10 2JF, S Yorkshire, England
Dale, M
;
Nicklin, MJH
论文数: 0引用数: 0
h-index: 0
机构:
Univ Sheffield, Royal Hallamshire Hosp, Div Mol & Genet Med, Sheffield S10 2JF, S Yorkshire, EnglandUniv Sheffield, Royal Hallamshire Hosp, Div Mol & Genet Med, Sheffield S10 2JF, S Yorkshire, England