Department of Microbiology and Immunology, Burns Institute, First Hospital Affiliated to the Chinese PLA General Hospital, Beijing, People's Republic of China.
J Interferon Cytokine Res. 2009 Oct;29(10):677-86. doi: 10.1089/jir.2008.0104.
High mobility group box-1 protein (HMGB1), a recently described late-acting cytokine that mediates lethality of sepsis and systemic inflammation, also plays a role in mediating dendritic cell (DC) maturation and activation. The present study was performed to clarify the effects of HMGB1 on splenic DCs and its potential regulating mechanism underlying T-cell-mediated immunity. DCs isolated from the spleens of normal rats were treated with HMGB1 of different dosage (0.1, 1, or 10 microg/mL) for different duration (24, 48, or 72 h). Expressions of co-stimulatory molecules, including CD80, CD86, and MHC-II on DCs surface, and cytokines, including interleukin (IL)-12, tumor necrosis factor (TNF)-alpha, were analyzed to identify DCs maturation and activation. The activated DCs were assessed for their capacity to stimulate the proliferation and differentiation of T cells. Expression of the receptor for advanced glycation end products (RAGE) on DCs and nuclear factor (NF)-kappaB activation in T lymphocytes were also determined. Stimulation with HMGB1 markedly up-regulated the co-stimulatory molecules and cytokines expressions, and they peaked at 48 h when DCs was treated with 1 microg/mL HMGB1. Treatment with anti-RAGE antibody prevented the maturation of DCs. DCs treated with HMGB1 (1 microg/mL for 48 h) promoted T-cell proliferation as well as differentiation, and markedly up-regulated IL-2, IL-2R expression and intranuclear NF-kappaB activation. The results suggested that HMGB1 appear to be a potential immunostimulatory signal that induced DC maturation and T-cell-mediated immunity, and RAGE was a potential receptor associated with maturation and differentiation of DCs. Moreover, HMGB1 might have a dual regulatory effect on immune functions of DCs varying with different concentration and stimulation time.
高迁移率族蛋白 B1（HMGB1）是一种新近描述的晚期细胞因子，介导脓毒症和全身炎症的致死性，也在调节树突状细胞（DC）成熟和激活中发挥作用。本研究旨在阐明 HMGB1 对脾 DC 的影响及其在 T 细胞介导免疫中的潜在调节机制。从正常大鼠脾脏中分离的 DC 用不同剂量（0.1、1 或 10μg/ml）的 HMGB1 处理不同时间（24、48 或 72 小时）。分析 DC 表面共刺激分子（包括 CD80、CD86 和 MHC-II）和细胞因子（包括白细胞介素-12（IL-12）、肿瘤坏死因子-α（TNF-α））的表达，以鉴定 DC 的成熟和激活。评估激活的 DC 刺激 T 细胞增殖和分化的能力。还测定了 DC 上的晚期糖基化终产物受体（RAGE）表达和 T 淋巴细胞中核因子（NF）-kappaB 的激活。HMGB1 的刺激明显上调了共刺激分子和细胞因子的表达，当 DC 用 1μg/ml 的 HMGB1 处理时，在 48 小时达到峰值。用抗 RAGE 抗体处理可防止 DC 的成熟。用 HMGB1（1μg/ml，48 小时）处理的 DC 促进了 T 细胞的增殖和分化，并显著上调了 IL-2、IL-2R 的表达和核内 NF-kappaB 的激活。结果表明，HMGB1 似乎是一种潜在的免疫刺激信号，诱导 DC 成熟和 T 细胞介导的免疫，RAGE 是与 DC 成熟和分化相关的潜在受体。此外，HMGB1 对 DC 免疫功能可能具有双重调节作用，其作用因浓度和刺激时间的不同而不同。
