KU812 cells provide a novel in vitro model of the human IL-33/ST2L axis: Functional responses and identification of signaling pathways

被引:20
作者
Tare, Nadine [1 ]
Li, Hongli [1 ]
Morschauser, Andrew [1 ]
Cote-Sierra, Javier [1 ]
Ju, Grace [1 ]
Renzetti, Louis [1 ]
Lin, Tai-An [1 ]
机构
[1] Hoffmann La Roche Inc, Pharma Res & Early Dev, Nutley, NJ 07110 USA
关键词
ST2; IL-33; IKK-2; NF-kappa B; Cytokine; Basophil; COLLAGEN-INDUCED ARTHRITIS; SOLUBLE ST2 PROTEIN; IL-1-LIKE CYTOKINE IL-33; N-TERMINAL KINASE; HUMAN MAST-CELLS; ACUTE EXACERBATION; RECEPTOR FAMILY; HUMAN BASOPHILS; TH2; CELLS; INHIBITOR;
D O I
10.1016/j.yexcr.2010.04.007
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
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.
引用
收藏
页码:2527 / 2537
页数:11
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