Role of Metallothionein in Post-Burn Inflammation

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• 作者：Wei Zhang ; Yongjun Xie ; Weihua Liu ; Xuefeng Xu ; Xuelian Chen ; Hairong Liu…
• 刊名：Inflammation
• 出版年：2016
• 出版时间：April 2016
• 年：2016
• 卷：39
• 期：2
• 页码：768-774
• 全文大小：396 KB
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• 作者单位：Wei Zhang (1)
  Yongjun Xie (2)
  Weihua Liu (1)
  Xuefeng Xu (1)
  Xuelian Chen (1)
  Hairong Liu (1)
  Yueming Liu (1)
  
  1. Burn and Plastic Surgery Department, The First Affiliated Hospital of Chengdu Medical College, 278 Baoguang Road, Xindu District, Chengdu, 610500, Sichuan, China
  2. Basic Medical College of Chengdu Medical College, Sichuan, China
  
• 刊物类别：Medicine
• 刊物主题：Medicine & Public Health
  Rheumatology
  Internal Medicine
  Pharmacology and Toxicology
  Pathology
  
• 出版者：Springer Netherlands
• ISSN：1573-2576

文摘

Metallothioneins (MTs) are a family of low molecular-weight and cysteine-rich metalloproteins that regulate metal metabolism and protect cells from oxygen free radicals. Recent studies suggested that MTs have some anti-inflammatory effects. However, the role of MTs in post-burn inflammation remains unclear. This study is designed to investigate the role of MTs in post-burn inflammation in a mouse burn model. MT-I/II null (−/−) and C57BL/6 wild-type (WT) mice were randomly divided into sham burn, burn, Zn treated, and Zn-MT-2 treated groups. The inflammatory cytokines levels were measured by enzyme-linked immunosorbent assay (ELISA). Myeloperoxidase (MPO) activity was determined by spectrophotometry. In in vitro study, exogenous MT-2 was added to macrophages that were stimulated with burn serum in the presence or absence of a p38 MAPK inhibitor SB203580. The IL-6 and TNF-α messenger RNA (mRNA) expression were detected by quantitative real-time polymerase chain reaction. The levels of p38 expression were determined by Western blot. Burn induced increased inflammatory cytokines such as interleukin (IL)-1β, IL-6, tumor necrosis factors-α, and macrophage chemoattractant protein-1 production in burn wound and serum. The MPO activities in the lung and heart were also increased after burn. These effects were significantly more prominent in MT (−/−) mice than in WT mice. Furthermore, these effects were inhibited by administration of exogenous MT-2 to both WT and MT (−/−) mice. Exogenous MT-2 inhibited the p38 expression and abrogated the increase of IL-6 and TNF-α mRNA expression from macrophages that were stimulated with burn serum. The effect of MT-2 was not further strengthened in the presence of SB203580. MTs may have a protective role against post-burn inflammation and inflammatory organ damage, at least partly through inhibiting the p38 MAPK signaling.