Burn-induced alterations in toll-like receptor-mediated responses by bronchoalveolar lavage cells.

Burn-induced alterations in toll-like receptor-mediated responses by bronchoalveolar lavage cells.
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DOI:
10.1016/j.cyto.2011.05.004
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发表时间:
2011-09
期刊:
影响因子:
3.8
通讯作者:
Schwacha, Martin G.
Schwacha, Martin G.
中科院分区:
医学3区
文献类型:
--
作者:
Oppeltz, Richard F.;Rani, Meenakshi;Zhang, Qiong;Schwacha, Martin G.
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烧伤与包括肺在内的多个器官床中的严重炎症和先天免疫系统的激活有关。类似地,Toll样受体(TLR)与先天免疫激活相关。尽管如此,目前还不清楚烧伤对TLR诱导的肺部炎症反应有什么影响。使雄性C57 BL/6小鼠经受烧伤(3度,25%TBSA)或假手术,并且在1、3或7天后,收集支气管肺泡灌洗(BAL)液,分离细胞并在体外用如下特异性TLR激动剂培养:酵母聚糖(TLR-2)、LPS(TLR-4)和CpG-ODN(TLR-9)。48小时后收集上清液,并通过Luminex测定炎性细胞因子水平(IL-1β、IL-6、IL-10、IL-17、TNF-α、KC、MCP-1、MIP-1α、MIP-1β和RANTES)。来自假手术和烧伤小鼠的BAL液不含可检测的细胞因子水平。BAL细胞,无论损伤,TLR-2和TLR-4活化。烧伤后7天,BAL细胞的TLR-2和TLR-4介导的反应增强,表现为IL-6、IL-17、TNF-α、MCP-1、MIP-1β和RANTES的产生增加。烧伤诱导TLR-2和TLR-4反应性的变化可能有助于烧伤后并发症的发展,如ALI和ARDS。
Burn is associated with profound inflammation and activation of the innate immune system in multiple organ beds, including the lung. Similarly, toll-like receptors (TLR) are associated with innate immune activation. Nonetheless, it is unclear what impact burn has on TLR-induced inflammatory responses in the lung. Male C57BL/6 mice were subjected to burn (3rd degree, 25% TBSA) or sham procedure and 1, 3 or 7 days thereafter, bronchoalveolar lavage (BAL) fluid was collected and cells were isolated and cultured in vitro with specific TLR agonists as follows: Zymosan (TLR-2), LPS (TLR-4) and CpG-ODN (TLR-9). Supernatants were collected 48 hr later and assayed for inflammatory cytokine levels (IL-1β, IL-6, IL-10, IL-17, TNF-α, KC, MCP-1, MIP-1α, MIP-1β and RANTES) by Luminex. BAL fluid from sham and burn mice did not contain detectable cytokine levels. BAL cells, irrespective of injury, were responsive to TLR-2 and TLR-4 activation. Seven days after burn, TLR-2 and TLR-4 mediated responses by BAL cells were enhanced as evidenced by increased production of IL-6, IL-17, TNF-α, MCP-1, MIP-1β and RANTES. Burn-induced changes in TLR-2 and TLR-4 reactivity may contribute to the development of post-burn complications, such as ALI and ARDS.
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