DJ-1 regulates mast cell activation and IgE-mediated allergic responses

JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY

卷:131

Article

Kim, Do Kyun¹  Kim, Hyuk Soon¹  Kim, A-Ram¹  Kim, Ji Hyung¹  Kim, Bokyung¹  Noh, Geunwoong²  Kim, Hyung Sik³  Beaven, Michael A.⁴  Kim, Young Mi⁵  Choi, Wahn Soo¹ 

[1] Konkuk Univ, Coll Med, Funct Genom Inst, Dept Immunol & Physiol, Chungju 380701, South Korea

[2] Chungnam Natl Univ Hosp, Dept Pediat, Subdiv Allergy & Clin Immunol, Taejon, South Korea

[3] Pusan Natl Univ, Coll Pharm, Pusan, South Korea

[4] NHLBI, Lab Mol Immunol, NIH, Bethesda, MD 20892 USA

[5] Duksung Womens Univ, Coll Pharm, Seoul, South Korea

关键词: DJ-1;    reactive oxygen species;    mast cells;    allergy;    Fc epsilon RI-mediated signals;   

DOI  :  10.1016/j.jaci.2012.10.012

来源: Elsevier

【 摘 要 】

Background: DJ-1 is an antioxidant protein known to reduce levels of reactive oxygen species (ROS), but its presence or function in mast cells and allergic diseases is unknown. Objectives: We sought to determine the role and mechanism of DJ-1 in allergic responses in vitro and in vivo. Methods: ROS and DJ-1 levels in serum or culture medium were measured with ELISA kits. The role of DJ-1 was evaluated in mast cell cultures and passive cutaneous anaphylaxis in normal or DJ-1 knockout (KO) mice. The mechanism of DJ-1 action was examined by using immunoblotting, immunoprecipitation, RT-PCR, and other molecular biological approaches. Results: Patients with atopic dermatitis had increased levels of ROS and diminished levels of DJ-1. DJ-1 KO mice exhibited enhanced passive cutaneous anaphylaxis and augmented ROS levels in sera and bone marrow-derived mast cells (BMMCs). Furthermore, antigen-induced degranulation and production of TNF-alpha and IL-4 were significantly amplified in DJ-1 KO and anti-DJ-1 small interfering RNA-transfected BMMCs compared with that seen in wild-type (WT) BMMCs. Studies with these cells and BMMCs transfected with small interfering RNAs against the phosphatases Src homology domain 2-containing protein tyrosine phosphatase (SHP) 1 and SHP-2 revealed that the DJ-1 KO phenotype could be attributed to suppression of SHP-1 activity and enhancement of SHP-2 activity, leading to strengthened signaling through linker for activation of T cells, phospholipase C gamma, and mitogen-activated protein kinases. Conclusions: A deficiency or constitutive activation of DJ-1 can have implications in mast cell-driven allergic diseases, such as asthma and anaphylaxis.

【 授权许可】

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