Dexamethasone and FK506 inhibit expression of distinct subsets of chemokines in human mast cells.
Dexamethasone and FK506 inhibit expression of distinct subsets of chemokines in human mast cells.
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DOI：
10.4049/jimmunol.0801375
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发表时间：
2009-06-01
期刊：
影响因子：
--
通讯作者：
Matsumoto K
中科院分区：
文献类型：
--
作者：
Kato A;Chustz RT;Ogasawara T;Kulka M;Saito H;Schleimer RP;Matsumoto K
肥大细胞通过Fc、ε、RI的交联产生大量的趋化因子，参与变态反应性疾病的发病。本研究的目的是全面研究FcεRI介导的人肥大细胞趋化因子的诱导以及糖皮质激素(地塞米松)和钙调神经磷酸酶抑制剂(FK506)的作用。人外周血源性肥大细胞在地塞米松或FK506存在的情况下用抗IgE抗体刺激。基因芯片检测基因表达谱，实时定量聚合酶链式反应证实基因表达谱，细胞微球阵列和酶联免疫吸附试验检测趋化因子浓度。抗IgE刺激可显著诱导肥大细胞表达8种趋化因子。地塞米松显著抑制抗IgE对CCL2、CCL7、CXCL3和CXCL8的诱导作用，而FK506则增强其诱导作用。相反，FK506可显著抑制CCL1、CCL3、CCL4和CCL18的诱导，但地塞米松可促进CCL1的诱导。地塞米松和FK506联合应用可抑制抗IgE刺激产生的所有趋化因子。使用蛋白水解酶抑制剂的研究表明，肥大细胞蛋白水解酶可以降解几种趋化因子。这些结果表明，皮质类固醇和钙调神经磷酸酶抑制剂抑制不同亚群的趋化因子的表达，这些药物的组合几乎完全抑制了所有趋化因子基因在人肥大细胞对FcεRI依赖刺激的诱导。这意味着在治疗肥大细胞衍生的趋化因子起主要作用的过敏性疾病方面，皮质类固醇和钙调神经磷酸酶抑制剂的组合可能比单独使用一种药物更有效。
Mast cells produce a large amount of several chemokines after cross-linking of FcεRI and participate in the pathogenesis of allergic diseases. The objective of this study was to comprehensively investigate FcεRI-mediated chemokine induction in human mast cells and the effect of a corticosteroid (dexamethasone) and a calcineurin inhibitor (FK506). Human peripheral blood-derived mast cells were stimulated with anti-IgE Ab in the presence of dexamethasone or FK506. Gene expression profiles were evaluated using GeneChip and confirmed by real-time PCR, and chemokine concentrations were measured by cytometric bead arrays and ELISA. Expression of eight chemokines was significantly induced in mast cells by anti-IgE stimulation. Induction of CCL2, CCL7, CXCL3, and CXCL8 by anti-IgE was significantly inhibited by dexamethasone but was enhanced by FK506. In contrast, induction of CCL1, CCL3, CCL4, and CCL18 was significantly inhibited by FK506 but, with the exception of CCL1, was enhanced by dexamethasone. Combination of dexamethasone and FK506 suppressed production of all chemokines by anti-IgE stimulation. Studies using protease inhibitors indicate that mast cell proteases may degrade several of the chemokines. These results suggest that corticosteroids and calcineurin inhibitors inhibit expression of distinct subsets of chemokines, and a combination of these drugs almost completely suppresses the induction of all chemokine genes in human mast cells in response to FcεRI-dependent stimulation. This implies that a combination of a corticosteroid and a calcineurin inhibitor may be more effective than each single agent for the treatment of allergic diseases in which mast cell-derived chemokines play a major role.
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影响因子：
24.3
作者：
Carroll, NG;Mutavdzic, S;James, AL
通讯作者：
James, AL
DOI：
10.1164/ajrccm.155.6.9196082
发表时间：
1997-06-01
影响因子：
24.7
作者：
Fahy, JV;Fleming, HE;Boushey, HA
通讯作者：
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影响因子：
6.5
作者：
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通讯作者：
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影响因子：
4.4
作者：
Gombert, M;Dieu-Nosjean, MC;Homey, B
通讯作者：
Homey, B
影响因子：
20.3
作者：
Iida, M;Matsumoto, K;Saito, H
通讯作者：
Saito, H