Objective： To observe the effects of Xuebijing Injection （血必净注射液） on dendritic cells （DCs） and T lymphocytes, and the potential mechanisms of its therapeutic effect on systemic lupus erythematosus （SLE）. Methods： A widely used mouse model, SLE-prone BLLF1 mice aged 8-10 weeks, was employed. Mice were randomly divided into 4 groups： a normal group, a model group and two treatment groups treated with Xuebijing Injection with a dose of 6.4 mL/kg via intraperitoneal administration for SLE-prone BLLF1 mice aged 8 weeks （treatment A group） and 10 weeks （treatment B group）. Renal tissue sections were stained with Masson＇s trichrome and periodic acid-silver methenamine. Histopathological changes in the kidney were evaluated by a light microscopy. The capacity of the DCs isolated from the spleen to stimulate the T cell proliferation in response to concanavalin A （Con A） was determined. Results： Compared with the model group, levels of anti-dsDNA antibodies in the two treatment groups decreased remarkablely （P〈0.01, P〈0.05）, and levels of serum creatinine and blood urea nitrogen increased （P〈0.01, P〈0.05）. Pathological changes were found in the kidney in the model group. Histopathological abnormalities were alleviated in the two treatment groups. Treatment with Xuebijing injection also significantly upregulated the expression of CD80, CD86 and major histocompatibility class Ⅱ by DCs compared with the model group （P〈0.05）. When splenic T lymphocytes from BLLF1 mice were co-cultured with DCs at ratios of 1：100, 1：150 and 1：200 for 3 and 5 days, the proliferation of T lymphocytes was suppressed compared with the normal group （P〈0.05）, but this was restored by Xuebijing Injection under the same conditions. In the model group, levels of tumor necrosis factor （TNF）-α in supernatants were significantly elevated compared with the normal group （P〈0.01）, interleukin-2 levels decreased （P〈0.05）, while these changes were significantly al
High mobility group box-1 protein(HMGB1),which is a nuclear protein,participates in chromatin architecture and transcriptional regulation.When released from cells,HMGB1 also plays a well-established role as a pro-inflammatory mediator during innate immune responses to injury.In the initial stage of injury,there is a release of large quantities of early pro-inflammatory mediators to initiate or perpetuate immune responses against pathogens,but this pro-inflammatory period is transient,and it is followed by a prolonged period of immune suppression.At present,several lines of evidences have suggested that HMGB1 is a late cytokine provoking delayed endotoxin morbidity,which may enhance the production of early proinflammatory mediators,and it can contribute potently to the activation of different immune cells and play a role in the development of host cell-mediated immunity.The biology of HMGB1 has been extensively studied as a pro-inflammatory cytokine of systemic inflammation,however,this review will attempt to provide a summary of the effects of HMGB1 on different immune cells and its regulatory mechanism in acute insults.
Ying-yi LUANFeng-hua YAOQing-hong ZHANGXiao-mei ZHUNing DONGYong-ming YAO
High mobility group box 1 protein （HMGB1） is a highly conserved, ubiquitous protein in the nuclei and cytoplasm of nearly all cell types. HMGB1 is secreted into the extracellular milieu and acts as a proinflammatory cytokine. In this article we reviewed briefly the cellular immune response mediated by HMGB1 in inflammation and sepsis. This systemic review is mainly based on our own work and other related reports HMGB1 can actively affect the immune functions of many types of cells including T lymphocytes, regulatory T cells （Tregs）, dendritic cells （DCs）, macrophages, and natural killer cells （NK cells）. Various cellular responses can be mediated by HMGB1 which binds to cell-surface receptors [e.g., the receptor for advanced glycation end products （RAGE）, Toll-like receptor （TLR）2, and TLR4]. Anti-HMGB1 treatment, such as anti-HMGB1 polyclonal or monoclonal antibodies, inhibitors （e.g., ethyl pyruvate） and antagonists （e.g., A box）, can protect against sepsis lethality and give a wider window for the treatment opportunity. HMGB1 is an attractive target for the development of new therapeutic strategies in the treatment of patients with septic complications.
