| Title : Omega-3 fatty acid epoxides are autocrine mediators that control the magnitude of IgE-mediated mast cell activation - Shimanaka_2017_Nat.Med_23_1287 |
| Author(s) : Shimanaka Y , Kono N , Taketomi Y , Arita M , Okayama Y , Tanaka Y , Nishito Y , Mochizuki T , Kusuhara H , Adibekian A , Cravatt BF , Murakami M , Arai H |
| Ref : Nat Med , 23 :1287 , 2017 |
|
Abstract :
Critical to the function of mast cells in immune responses including allergy is their production of lipid mediators, among which only omega-6 (omega-6) arachidonate-derived eicosanoids have been well characterized. Here, by employing comprehensive lipidomics, we identify omega-3 (omega-3) fatty acid epoxides as new mast cell-derived lipid mediators and show that they are produced by PAF-AH2, an oxidized-phospholipid-selective phospholipase A2. Genetic or pharmacological deletion of PAF-AH2 reduced the steady-state production of omega-3 epoxides, leading to attenuated mast cell activation and anaphylaxis following FcvarepsilonRI cross-linking. Mechanistically, the omega-3 epoxides promote IgE-mediated activation of mast cells by downregulating Srcin1, a Src-inhibitory protein that counteracts FcvarepsilonRI signaling, through a pathway involving PPARg. Thus, the PAF-AH2-omega-3 epoxide-Srcin1 axis presents new potential drug targets for allergic diseases. |
| PubMedSearch : Shimanaka_2017_Nat.Med_23_1287 |
| PubMedID: 29035365 |
| Gene_locus related to this paper: human-PAFAH2 |
| Inhibitor | AA39-2 |
| Gene_locus | human-PAFAH2 |
Shimanaka Y, Kono N, Taketomi Y, Arita M, Okayama Y, Tanaka Y, Nishito Y, Mochizuki T, Kusuhara H, Adibekian A, Cravatt BF, Murakami M, Arai H (2017)
Omega-3 fatty acid epoxides are autocrine mediators that control the magnitude of IgE-mediated mast cell activation
Nat Med
23 :1287
Shimanaka Y, Kono N, Taketomi Y, Arita M, Okayama Y, Tanaka Y, Nishito Y, Mochizuki T, Kusuhara H, Adibekian A, Cravatt BF, Murakami M, Arai H (2017)
Nat Med
23 :1287