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Mycophenolate mofetil and triptolide alleviating airway inflammation in asthmatic model mice partly by inhibiting bone marrow eosinophilopoiesis

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机构: [1]Sichuan Univ, W China Hosp, Key Lab Transplantat Engn & Immunol, Chengdu 610041, Peoples R China [2]Sichuan Univ, W China Hosp, Dept Resp Med, Chengdu 610041, Peoples R China [3]Henan Coll Tradit Chinese Med, Affiliated Hosp 1, Dept Resp Med, Zhengzhou, Peoples R China
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关键词: CYCLOSPORINE-A ALLERGIC INFLAMMATION PROGENITOR CELLS IL-5 RECEPTOR IN-VITRO INTERLEUKIN-5 EXPRESSION CHEMOKINE PHARMACOKINETICS PROLIFERATION

摘要:
The bone marrow eosinophilopoiesis makes a major contribution to the chronic airway inflammation in asthmatic animals and patients. Some anti-asthmatic medicines alleviated the asthmatic airway inflammation by inhibiting the bone marrow eosinophilopoiesis. Immunosuppressive agents have been commonly used in patients with glucocorticoid refractory asthma and have been proved to be effective. However, the research on the effect of the immunosuppressive agents on the bone marrow eosinophilopoiesis has seldom been reported. The purpose of the study was to explore the effect of mycophenolate mofetil (MMF) and triptolide (TP) on the bone marrow eosinophilopoiesis and to further investigate the mechanisms of the immunosuppressive agents involved in the anti-asthmatic effect. Balb/c mice were sensitized and challenged by OVA to establish the asthmatic model, and respectively administered orally with sterile saline, MMIF, and TP once daily for 2 weeks. Airway inflammation, and inflammatory mediators IL-5 and eotaxin in the peripheral blood and bone marrow were measured by histology and ELISA. Immunocytochemistry combined with in situ hybridization technique and Western blot analysis was performed to estimate the amount of CD34+ IL-5R alpha mRNA(+) cells and IL-5R alpha expression in the bone marrow. The count of new produced eosinophils in the bone marrow was detected by anti-BrdU immunocytochemistry. We found that MMF and TP attenuated OVA-induced eosinophil (EOS) recruitment in bronchoalveolar lavage fluid (BALF), inflammatory mediator expression of IL-5 and eotaxin in the peripheral blood, inflammatory cells expressing eotaxin in the lung tissues and the number of new produced EOS in the bone marrow. Also, MMF abated the migration of CD34+ cells from the bone marrow to the peripheral blood, which was associated with a decreased eotaxin expression in the bone marrow and a decreased CCR3 expression on bone marrow cells. White, MMF or TP failed to decrease the amount of CD34+ IL-5R alpha mRNA(+) cells (EOS progenitors), and IL-5R alpha expression in the bone marrow of asthmatic model mice. These results demonstrated that MMF and TP reduce the eosinophilopoiesis of the bone marrow; this is associated with a decrease of IL-5 produced by T cells, which contribute to alleviate the allergic airway inflammation in asthma. In addition, MMIF decreased the CD34+ cells migration from the bone marrow to the peripheral blood by the reduction of the level of eotaxin in the bone marrow and the expression of CCR3 on the bone marrow cells. (C) 2008 Elsevier B.V. All rights reserved.

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出版当年[2008]版:
大类 | 3 区 医学
小类 | 4 区 免疫学 4 区 药学
最新[2023]版:
大类 | 2 区 医学
小类 | 2 区 免疫学 2 区 药学
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出版当年[2008]版:
Q3 PHARMACOLOGY & PHARMACY Q3 IMMUNOLOGY
最新[2023]版:
Q1 PHARMACOLOGY & PHARMACY Q2 IMMUNOLOGY

影响因子: 最新[2023版] 最新五年平均 出版当年[2008版] 出版当年五年平均 出版前一年[2007版] 出版后一年[2009版]

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第一作者机构: [2]Sichuan Univ, W China Hosp, Dept Resp Med, Chengdu 610041, Peoples R China
通讯机构: [1]Sichuan Univ, W China Hosp, Key Lab Transplantat Engn & Immunol, Chengdu 610041, Peoples R China [*1]Sichuan Univ, W China Hosp, Key Lab Transplantat Engn & Immunol, Chengdu 610041, Peoples R China
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