| First Author | Kim DK | Year | 2013 |
| Journal | J Allergy Clin Immunol | Volume | 131 |
| Issue | 6 | Pages | 1653-62 |
| PubMed ID | 23182168 | Mgi Jnum | J:330090 |
| Mgi Id | MGI:6837145 | Doi | 10.1016/j.jaci.2012.10.012 |
| Citation | Kim DK, et al. (2013) DJ-1 regulates mast cell activation and IgE-mediated allergic responses. J Allergy Clin Immunol 131(6):1653-62 |
| abstractText | 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 Cgamma, 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. |
