Kalyan Shirin, Chow Anthony W
Vancouver Hospital & Health Sciences, Diamond Health Care Centre, Department of Medicine, Vancouver, BC, Canada V5Z1M9.
Mediators Inflamm. 2008;2008:512196. doi: 10.1155/2008/512196. Epub 2008 Nov 4.
High mobility group box-1 (HMGB-1) is a DNA-binding protein secreted by activated monocytes and has been identified as a key late mediator of endotoxic shock. We investigated the regulation of HMGB-1 in human peripheral blood mononuclear cells (PBMCs) following stimulation with the staphylococcal superantigen, toxic shock syndrome toxin-1 (TSST-1), and found that TSST-1, like LPS, induced the secretion of HMGB-1 from human PBMC. However, unlike monocyte-driven sepsis caused by endotoxin, translocation and secretion of HMGB-1 mediated by TSST-1 was dependent on the presence of both activated T cells and monocytes. Furthermore, we show that nuclear HMGB-1 is released from TSST-1 stimulated T cells. This finding presents a basis for investigating the potential of targeting HMGB-1 for the treatment of toxic shock syndrome, and provides further insight on the role of HMGB-1 in the cross-talk between activated monocytes and T cells.
高迁移率族蛋白B1（HMGB-1）是一种由活化单核细胞分泌的DNA结合蛋白，已被确定为内毒素休克的关键晚期介质。我们研究了葡萄球菌超抗原中毒性休克综合征毒素-1（TSST-1）刺激后人外周血单核细胞（PBMCs）中HMGB-1的调节情况，发现TSST-1与脂多糖（LPS）一样，可诱导人PBMC分泌HMGB-1。然而，与内毒素引起的单核细胞驱动的败血症不同，TSST-1介导的HMGB-1易位和分泌依赖于活化T细胞和单核细胞的同时存在。此外，我们发现核HMGB-1从TSST-1刺激的T细胞中释放出来。这一发现为研究靶向HMGB-1治疗中毒性休克综合征的潜力提供了依据，并进一步深入了解了HMGB-1在活化单核细胞与T细胞相互作用中的作用。
