Phospholipase cε, an effector of ras and rap small GTPases, is required for airway inflammatory response in a mouse model of bronchial asthma.
Phospholipase cε, an effector of ras and rap small GTPases, is required for airway inflammatory response in a mouse model of bronchial asthma.
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DOI：
10.1371/journal.pone.0108373
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发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Kataoka T
中科院分区：
文献类型：
--
作者：
Nagano T;Edamatsu H;Kobayashi K;Takenaka N;Yamamoto M;Sasaki N;Nishimura Y;Kataoka T
磷脂酶Cε(PLCε)是Ras和Rap小分子GTP酶的效应物，在非免疫细胞中表达。已经证实，PLCε通过上调角质形成细胞和真皮成纤维细胞产生炎症细胞因子，在皮肤炎症中发挥重要作用，如佛波酯涂抹或紫外线照射引起的皮肤炎症以及T辅助细胞(Th)1细胞介导的接触性皮炎。然而，关于PLCε是否参与调节呼吸系统的炎症，如Th2细胞介导的过敏性哮喘，人们知之甚少。我们用PLCε+/+小鼠和PLCεΔX/ΔX突变小鼠制备了过敏性哮喘小鼠模型，其中PLCε催化失活。用卵白蛋白免疫不同ε基因的小鼠，然后用含有卵白蛋白的气雾剂激发，通过分析气道高反应性、支气管肺泡灌洗液、炎性细胞因子水平和卵清蛋白特异性免疫球蛋白(Ig)水平来评估哮喘反应。用原代培养的支气管上皮细胞检测PLCε基因对细胞因子产生的影响。卵清蛋白攻击后，卵清蛋白免疫的εΔX/ΔX小鼠的气道高反应性和支气管炎明显减轻，并伴随着支气管肺泡灌洗液中Th2型细胞因子含量的降低。相反，卵清蛋白特异性免疫球蛋白和免疫球蛋白E水平不受PLCε基因的影响，提示致敏作用不依赖于PLCε。在受到攻击的小鼠中，PLCε缺乏减少了支气管上皮细胞中促炎细胞因子的产生。从PLCεΔX/ΔX小鼠制备的原代培养的支气管上皮细胞在肿瘤坏死因子-α刺激下的促炎细胞因子的产生减少，提示PLCεΔX/ΔX小鼠的细胞因子产生减少是由于PLCε缺乏所致。PLCε通过上调支气管上皮细胞产生炎性细胞因子，在哮喘发病机制中发挥重要作用。
Phospholipase Cε (PLCε) is an effector of Ras and Rap small GTPases and expressed in non-immune cells. It is well established that PLCε plays an important role in skin inflammation, such as that elicited by phorbol ester painting or ultraviolet irradiation and contact dermatitis that is mediated by T helper (Th) 1 cells, through upregulating inflammatory cytokine production by keratinocytes and dermal fibroblasts. However, little is known about whether PLCε is involved in regulation of inflammation in the respiratory system, such as Th2-cells-mediated allergic asthma. We prepared a mouse model of allergic asthma using PLCε +/+ mice and PLCε ΔX/ΔX mutant mice in which PLCε was catalytically-inactive. Mice with different PLCε genotypes were immunized with ovalbumin (OVA) followed by the challenge with an OVA-containing aerosol to induce asthmatic response, which was assessed by analyzing airway hyper-responsiveness, bronchoalveolar lavage fluids, inflammatory cytokine levels, and OVA-specific immunoglobulin (Ig) levels. Effects of PLCε genotype on cytokine production were also examined with primary-cultured bronchial epithelial cells. After OVA challenge, the OVA-immunized PLCε ΔX/ΔX mice exhibited substantially attenuated airway hyper-responsiveness and broncial inflammation, which were accompanied by reduced Th2 cytokine content in the bronchoalveolar lavage fluids. In contrast, the serum levels of OVA-specific IgGs and IgE were not affected by the PLCε genotype, suggesting that sensitization was PLCε-independent. In the challenged mice, PLCε deficiency reduced proinflammatory cytokine production in the bronchial epithelial cells. Primary-cultured bronchial epithelial cells prepared from PLCε ΔX/ΔX mice showed attenuated pro-inflammatory cytokine production when stimulated with tumor necrosis factor-α, suggesting that reduced cytokine production in PLCε ΔX/ΔX mice was due to cell-autonomous effect of PLCε deficiency. PLCε plays an important role in the pathogenesis of bronchial asthma through upregulating inflammatory cytokine production by the bronchial epithelial cells.
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DOI：
10.1161/atvbaha.109.191395
发表时间：
2010-03
期刊：
Arteriosclerosis, thrombosis, and vascular biology
影响因子：
--
作者：
Lötzer K;Döpping S;Connert S;Gräbner R;Spanbroek R;Lemser B;Beer M;Hildner M;Hehlgans T;van der Wall M;Mebius RE;Lovas A;Randolph GJ;Weih F;Habenicht AJ
通讯作者：
Habenicht AJ
影响因子：
2.1
作者：
DEJONG, PM;VANSTERKENBURG, MAJA;PONEC, M
通讯作者：
PONEC, M
影响因子：
3.7
作者：
Jang S;Morris S;Lukacs NW
通讯作者：
Lukacs NW
影响因子：
11.2
作者：
Ikuta, Shuzo;Edamatsu, Hironori;Kataoka, Tohru
通讯作者：
Kataoka, Tohru
影响因子：
4.8
作者：
Huang, Weigang;Barrett, Matthew;Zhang, Qisheng
通讯作者：
Zhang, Qisheng