Abstract
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.
Highlights
High mobility group box-1 (HMGB-1) protein is a 30 kDa nonhistone nuclear DNA binding protein that is shown to have an extracellular role in inflammation, cell differentiation, adherence, and motility [1,2,3]
Our finding that HMGB-1 is secreted by T cells following toxic shock syndrome toxin-1 (TSST-1) stimulation may parallel the observation made by Semino et al [22] who found that distinct NK cell subsets secreted HMGB-1 which served to differentiate autologous dendritic cells, and this event was modulated by environmental stimuli
HMGB-1 was shown to induce monocytes to differentiate into dendritic cells that polarized T cells to give a Th1 response [19], a feature characteristic of the effect of TSST-1 stimulation on human peripheral blood mononuclear cells (PBMCs)
Summary
High mobility group box-1 (HMGB-1) protein is a 30 kDa nonhistone nuclear DNA binding protein that is shown to have an extracellular role in inflammation, cell differentiation, adherence, and motility [1,2,3]. Extracellular HMGB1 was initially identified as amphoterin, a heparin-binding protein promoting neurite outgrowth in the perinatal rat brain [4]. Activated macrophages and monocytes secrete this inflammatory molecule by a process requiring acetylation of the protein, which permits its translocation from the nucleus to secretory lysosomes [8]. Neutralizing antibodies directed at HMGB-1 rescued mice from lethal endotoxemia even when administered 24 hours after sepsis initiation [7, 9]. For these reasons, HMGB-1 is viewed as an attractive therapeutic target for various inflammatory disorders including endotoxic shock [10]
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
