Modulation of cytokine and nitric oxide by mesenchymal stem cell transfer in lung injury/fibrosis.
Modulation of cytokine and nitric oxide by mesenchymal stem cell transfer in lung injury/fibrosis.
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DOI：
10.1186/1465-9921-11-16
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发表时间：
2010-02-08
影响因子：
5.8
通讯作者：
Park CS
中科院分区：
文献类型：
--
作者：
Lee SH;Jang AS;Kim YE;Cha JY;Kim TH;Jung S;Park SK;Lee YK;Won JH;Kim YH;Park CS
目前不存在对急性肺损伤和纤维化的有效治疗。本研究的目的是研究骨髓间充质干细胞（BMDMSCs）对博莱霉素（BLM）诱导的急性肺损伤和纤维化以及一氧化氮代谢产物和炎性细胞因子产生的时间依赖性影响。BLM吸入后4天转移BMDMSC。分析湿/干比、支气管肺泡灌洗液细胞特征、组织学变化和胶原沉积。每周测量亚硝酸盐、硝酸盐和细胞因子直到第28天。在第7天，与假手术大鼠相比，BLM治疗大鼠的湿/干比、嗜酸性炎症和胶原蛋白量升高（p = 0.05-0.002）。亚硝酸盐、硝酸盐、IL-1β、IL-6、TNF-α、TGF-β和VEGF水平在第7天也较高（p < 0.05）。淋巴细胞和巨噬细胞浸润程度随时间稳步增加。BMDMSC移植显著降低BLM诱导的湿/干比、嗜酸性浸润程度、胶原沉积以及细胞因子、亚硝酸盐和硝酸盐水平的增加（p < 0.05）。荧光原位杂交将移植的细胞定位于肺损伤区域。BMDMSCs的全身转移通过下调一氧化氮代谢产物、促炎细胞因子和血管生成细胞因子有效地减少了BLM诱导的肺损伤和纤维化。
No effective treatment for acute lung injury and fibrosis currently exists. Aim of this study was to investigate the time-dependent effect of bone marrow-derived mesenchymal stem cells (BMDMSCs) on bleomycin (BLM)-induced acute lung injury and fibrosis and nitric oxide metabolites and inflammatory cytokine production. BMDMSCs were transferred 4 days after BLM inhalation. Wet/dry ratio, bronchoalveolar lavage cell profiles, histologic changes and deposition of collagen were analyzed. Nitrite, nitrate and cytokines were measured weekly through day 28. At day 7, the wet/dry ratio, neutrophilic inflammation, and amount of collagen were elevated in BLM-treated rats compared to sham rats (p = 0.05-0.002). Levels nitrite, nitrate, IL-1β, IL-6, TNF-α, TGF-β and VEGF were also higher at day 7 (p < 0.05). Degree of lymphocyte and macrophage infiltration increased steadily over time. BMDMSC transfer significantly reduced the BLM-induced increase in wet/dry ratio, degree of neutrophilic infiltration, collagen deposition, and levels of the cytokines, nitrite, and nitrate to those in sham-treated rats (p < 0.05). Fluorescence in situ hybridization localized the engrafted cells to areas of lung injury. Systemic transfer of BMDMSCs effectively reduced the BLM-induced lung injury and fibrosis through the down-regulation of nitric oxide metabolites, and proinflammatory and angiogenic cytokines.
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影响因子：
4.4
作者：
Gupta, Naveen;Su, Xiao;Matthay, Michael A.
通讯作者：
Matthay, Michael A.
DOI：
10.1165/ajrcmb.21.1.3379
发表时间：
1999-07-01
影响因子：
6.4
作者：
Bellocq, A;Azoulay, E;Baud, L
通讯作者：
Baud, L
DOI：
10.1165/ajrcmb.22.6.3779
发表时间：
2000-06-01
影响因子：
6.4
作者：
Kaner, RJ;Ladetto, JV;Crystal, RG
通讯作者：
Crystal, RG
影响因子：
--
作者：
BarcellosHoff, MH;Dix, TA
通讯作者：
Dix, TA
DOI：
10.1165/ajrcmb.16.1.8998084
发表时间：
1997-01-01
影响因子：
6.4
作者：
Hagimoto, N;Kuwano, K;Hara, N
通讯作者：
Hara, N