HMGB1 as a drug target in staphylococcal pneumonia.

HMGB1 as a drug target in staphylococcal pneumonia.
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DOI:
10.1186/cc13810
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发表时间:
2014-03-31
期刊:
Critical care (London, England)
影响因子:
--
通讯作者:
Fink MP
Fink MP
中科院分区:
其他
文献类型:
--
作者:
Fink MP

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高迁移率族蛋白(HMGB)1是一种小的DNA结合蛋白。在细胞核中,HMGB1在基因表达和DNA复制中起作用。当它被释放或分泌到细胞外环境中时,HMGB1作为促炎性类尼古丁介质发挥作用。最近报道的数据支持这样的观点,即在由金黄色葡萄球菌致病菌株引起的肺炎小鼠模型中,用中和性抗HMGB1抗体治疗可改善肺损伤。这些发现表明,HMGB1可能是科学家,临床研究人员和制药公司寻求开发更好的药物治疗葡萄球菌肺炎的重要药物靶标。然而,不幸的是,令人鼓舞的结果,从人类疾病的小鼠模型往往不能转化为积极的发现,在临床试验中。因此,在从临床前研究进入临床研究之前,通过使用大型肺炎动物模型进行额外的研究来验证和扩展最近的实验结果可能是谨慎的。
High mobility group box (HMGB)1 is a small DNA-binding protein. In the nucleus, HMGB1 plays a role in gene expression and DNA replication. When it is released or secreted into the extracellular milieu, HMGB1 functions as a pro-inflammatory cytokine-like mediator. Recently reported data support the view that treatment with a neutralizing anti-HMGB1 antibody ameliorated pulmonary damage in a murine model of pneumonia caused by a pathogenic strain of Staphylococcus aureus. These findings suggest that HMGB1 may be an important drug target as scientists, clinical investigators and pharmaceutical companies seek to develop better agents for the treatment of staphylococcal pneumonia. Unfortunately, however, encouraging results from murine models of human disease often fail to translate into positive findings in clinical trials. Thus, before moving from pre-clinical into clinical studies, it may be prudent to validate and extend the recent experimental findings by carrying out additional studies, using a large animal model of pneumonia.
DOI: 10.1073/pnas.1222878110
发表时间: 2013-02-26
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