Prolonged Treatment with Inhaled Corticosteroids does not Normalize High Activity of Matrix Metalloproteinase-9 in Exhaled Breath Condensates of Children with Asthma.

Prolonged Treatment with Inhaled Corticosteroids does not Normalize High Activity of Matrix Metalloproteinase-9 in Exhaled Breath Condensates of Children with Asthma.
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用吸入的皮质类固醇长期治疗在哮喘儿童的呼出呼吸冷凝物中,基质金属蛋白酶9的高活性并不能使其正常化。

DOI:
10.1007/s00005-015-0328-z
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发表时间:
2015-06
影响因子:
3.2
通讯作者:
Grzela, Tomasz
Grzela, Tomasz
中科院分区:
医学4区
文献类型:
--
作者:
Grzela, Katarzyna;Zagorska, Wioletta;Krejner, Alicja;Litwiniuk, Malgorzata;Zawadzka-Krajewska, Anna;Banaszkiewicz, Aleksandra;Kulus, Marek;Grzela, Tomasz

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哮喘气道重塑与基质金属蛋白酶(MMP)-9水平升高有关。MMP-9在哮喘患者的粘膜活检、痰液和呼出气冷凝物(EBC)中均呈高水平表达。然而,没有关于真实的体内活性的数据。吸入性皮质类固醇在哮喘控制中是有效的,但尚不清楚它们是否仅减轻炎症,或也防止呼吸道进行性重塑。因此,本研究的目的是评估MMP-9在促炎细胞因子(IL-6,IL-8和肿瘤坏死因子,TNF)的背景下的量和活性,在哮喘儿童的EBC中测量,用吸入性类固醇治疗。该研究涉及27名哮喘儿童,持续吸入丙酸氟替卡松治疗,22名健康对照。除了常规的临床筛选,在EBC中选择的细胞因子进行了分析,使用超灵敏ELISA,而MMP-9的活性进行了评估,使用一种新的免疫酶谱法。尽管长期吸入类固醇治疗,但哮喘组MMP-9/EBC活性显著高于健康对照组。此外,高MMP-9/EBC在哮喘患儿与IgE血清水平显着相关。在所有EBC样品中,IL-6和IL-8浓度低于检测限。TNF/EBC水平在哮喘和健康儿童中相似。我们推测哮喘中MMP-9的过度活跃可能与高IgE血清水平密切相关。我们的研究结果表明,吸入类固醇可能是无效的,以防止哮喘相关的气道重塑。最后,我们强调了进一步研究MMP-9抑制剂在哮喘治疗中的必要性。
The airway remodeling in asthma is associated with increased amount of matrix metalloproteinase (MMP)-9. High levels of MMP-9 were found in mucosal biopsies, sputum and in exhaled breath condensates (EBC) of asthma patients. However, there are no data concerning real in vivo activity. Inhaled corticosteroids are effective in asthma control, but it is unclear, whether they only attenuate inflammation, or also protect against progressive remodeling of respiratory tract. Therefore, the aim of the study was to assess the amount and activity of MMP-9 in context of pro-inflammatory cytokines (IL-6, IL-8 and tumor necrosis factor, TNF), measured in EBC of asthma-suffering children, treated with inhaled steroids. The study involved 27 children with asthma, continuously treated with inhaled fluticasone propionate, and 22 healthy controls. In addition to routine clinical screening, the selected cytokines in EBC were analyzed using Ultrasensitive ELISA, whereas activity of MMP-9 was assessed using a novel immunozymography method. Despite chronic treatment with inhaled steroids mean MMP-9/EBC activity in asthma group was significantly higher than in healthy controls. Moreover, high MMP-9/EBC in asthma-suffering children significantly correlated with IgE serum levels. The IL-6 and IL-8 concentration was below the detection limit in all EBC samples. TNF/EBC levels were similar in both, asthma and healthy children. We hypothesize that MMP-9 hyperactivity in asthma may be closely related to high IgE serum levels. Our results suggest that inhaled steroids may be ineffective to prevent asthma-associated airway remodeling. Finally, we emphasize the necessity of further research focused on MMP-9 inhibition in asthma treatment.
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