Lymphoid tissue phospholipase A2 group IID resolves contact hypersensitivity by driving antiinflammatory lipid mediators.
Lymphoid tissue phospholipase A2 group IID resolves contact hypersensitivity by driving antiinflammatory lipid mediators.
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淋巴组织磷脂酶A2组IID通过驱动抗炎脂质介质来解决接触性超敏反应。
DOI：
10.1084/jem.20121887
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发表时间：
2013-06-03
期刊：
影响因子：
--
通讯作者：
Murakami M
中科院分区：
文献类型：
--
作者：
Miki Y;Yamamoto K;Taketomi Y;Sato H;Shimo K;Kobayashi T;Ishikawa Y;Ishii T;Nakanishi H;Ikeda K;Taguchi R;Kabashima K;Arita M;Arai H;Lambeau G;Bollinger JM;Hara S;Gelb MH;Murakami M
PLA2G2D通过动员促溶脂质介质改善皮肤炎症。炎症的消退是一个积极的过程，部分是由抗炎脂质介质介导的。尽管磷脂酶A2 （PLA2）酶通过动员脂质介质参与促进炎症，但PLA2亚型在抗炎脂质介质上游作用的分子实体尚不清楚。本研究表明，分泌的PLA2组IID （PLA2G2D）优先在CD11c+树突状细胞（dc）和巨噬细胞中表达，并显示出促分解功能。在半抗原诱导的接触性皮炎中，在Pla2g2d缺陷小鼠（Pla2g2d−/−）的皮肤和LNs中，炎症的消退而不是繁殖受到损害，其中免疫平衡从抗炎状态转向促炎状态。Pla2g2d - / -小鼠骨髓来源的dc在静脉转移到小鼠后被过度激活并引发皮肤炎症。脂质组学分析显示，LNs中的PLA2G2D有助于动员多不饱和脂肪酸池，这些脂肪酸可以作为抗炎/促溶解脂质介质（如resolvin D1和15-deoxy-Δ12,14-prostaglandin J2）的前体，从而减少LN细胞或dc中Th1细胞因子的产生和表面MHC类II的表达。总之，我们的研究结果强调了PLA2G2D作为一种“溶解sPLA2”，通过动员促溶解脂质介质来改善炎症，并指出这种酶在治疗炎症性疾病方面的潜在用途。
PLA2G2D ameliorates skin inflammation through mobilizing pro-resolving lipid mediators. Resolution of inflammation is an active process that is mediated in part by antiinflammatory lipid mediators. Although phospholipase A2 (PLA2) enzymes have been implicated in the promotion of inflammation through mobilizing lipid mediators, the molecular entity of PLA2 subtypes acting upstream of antiinflammatory lipid mediators remains unknown. Herein, we show that secreted PLA2 group IID (PLA2G2D) is preferentially expressed in CD11c+ dendritic cells (DCs) and macrophages and displays a pro-resolving function. In hapten-induced contact dermatitis, resolution, not propagation, of inflammation was compromised in skin and LNs of PLA2G2D-deficient mice (Pla2g2d−/−), in which the immune balance was shifted toward a proinflammatory state over an antiinflammatory state. Bone marrow-derived DCs from Pla2g2d−/− mice were hyperactivated and elicited skin inflammation after intravenous transfer into mice. Lipidomics analysis revealed that PLA2G2D in the LNs contributed to mobilization of a pool of polyunsaturated fatty acids that could serve as precursors for antiinflammatory/pro-resolving lipid mediators such as resolvin D1 and 15-deoxy-Δ12,14-prostaglandin J2, which reduced Th1 cytokine production and surface MHC class II expression in LN cells or DCs. Altogether, our results highlight PLA2G2D as a “resolving sPLA2” that ameliorates inflammation through mobilizing pro-resolving lipid mediators and points to a potential use of this enzyme for treatment of inflammatory disorders.
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影响因子：
4.8
作者：
Ishizaki, J;Suzuki, N;Hanasaki, K
通讯作者：
Hanasaki, K
DOI：
10.1084/jem.192.12.1685
发表时间：
2000-12-18
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
den Haan JM;Lehar SM;Bevan MJ
通讯作者：
Bevan MJ
影响因子：
1.9
作者：
Bowton, DL;Dmitrienko, AA;Sides, GD
通讯作者：
Sides, GD
影响因子：
4.4
作者：
Balestrieri, Barbara;Maekawa, Akiko;Arm, Jonathan P.
通讯作者：
Arm, Jonathan P.
影响因子：
4.4
作者：
Giannattasio, Giorgio;Fujioka, Daisuke;Balestrieri, Barbara
通讯作者：
Balestrieri, Barbara