title: DJ-1 regulates mast cell activation and IgE-mediated allergic responses.
abstract: 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.
  
  
  OBJECTIVE
  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-α 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 Cγ, 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.
authors.affiliation: Department of Immunology and Physiology, Functional Genomics Institute, College of Medicine, Konkuk University, Chungju, Korea.
authors.forename: Do Kyun
authors.initials: DK
authors.lastname: Kim
authors.forename: Hyuk Soon
authors.initials: HS
authors.lastname: Kim
authors.forename: A-Ram
authors.initials: AR
authors.lastname: Kim
authors.forename: Ji Hyung
authors.initials: JH
authors.lastname: Kim
authors.forename: Bokyung
authors.initials: B
authors.lastname: Kim
authors.forename: Geunwoong
authors.initials: G
authors.lastname: Noh
authors.forename: Hyung Sik
authors.initials: HS
authors.lastname: Kim
authors.forename: Michael A
authors.initials: MA
authors.lastname: Beaven
authors.forename: Young Mi
authors.initials: YM
authors.lastname: Kim
authors.forename: Wahn Soo
authors.initials: WS
authors.lastname: Choi
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism; D000293:Adolescent; D000328:Adult; D000818:Animals; D000941:Antigens / Q000276:immunology; D001854:Bone Marrow Cells / Q000276:immunology / Q000378:metabolism; D015550:Cell Degranulation / Q000276:immunology; D002648:Child; D002675:Child, Preschool; D016207:Cytokines / Q000096:biosynthesis; D003876:Dermatitis, Atopic / Q000276:immunology / Q000378:metabolism; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D006969:Hypersensitivity, Immediate / Q000235:genetics / Q000276:immunology* / Q000378:metabolism*; D015847:Interleukin-4 / Q000378:metabolism; D047908:Intracellular Signaling Peptides and Proteins / Q000097:blood / Q000235:genetics / Q000378:metabolism*; D008297:Male; D008407:Mast Cells / Q000276:immunology* / Q000378:metabolism*; D008565:Membrane Proteins / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D008875:Middle Aged; D015513:Oncogene Proteins / Q000097:blood / Q000235:genetics / Q000378:metabolism*; D010323:Passive Cutaneous Anaphylaxis; D010750:Phosphoproteins / Q000378:metabolism; D010766:Phosphorylation; D000071617:Protein Deglycase DJ-1; D054592:Protein Tyrosine Phosphatase, Non-Receptor Type 11 / Q000378:metabolism; D053824:Protein Tyrosine Phosphatase, Non-Receptor Type 6 / Q000378:metabolism; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D051076:Proto-Oncogene Proteins c-fyn / Q000378:metabolism; D034622:RNA Interference; D017382:Reactive Oxygen Species / Q000378:metabolism; D017455:Receptors, IgE / Q000378:metabolism; D015398:Signal Transduction; D000072377:Syk Kinase; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D055815:Young Adult
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D000941:Antigens; D016207:Cytokines; D047908:Intracellular Signaling Peptides and Proteins; C491734:Lat protein, mouse; D008565:Membrane Proteins; D015513:Oncogene Proteins; D010750:Phosphoproteins; D017382:Reactive Oxygen Species; D017455:Receptors, IgE; D014409:Tumor Necrosis Factor-alpha; D015847:Interleukin-4; D011505:Protein-Tyrosine Kinases; D051076:Proto-Oncogene Proteins c-fyn; C000606896:SYK protein, human; D000072377:Syk Kinase; C000606897:Syk protein, mouse; C105131:PARK7 protein, human; D000071617:Protein Deglycase DJ-1; D054592:Protein Tyrosine Phosphatase, Non-Receptor Type 11; D053824:Protein Tyrosine Phosphatase, Non-Receptor Type 6