Department of Respiratory, Inflammation and Autoimmune Disease, MedImmune, Gaithersburg, Maryland 20878, USA.
Annu Rev Immunol. 2010;28:367-88. doi: 10.1146/annurev.immunol.021908.132603.
The immune system has evolved to respond not only to pathogens, but also to signals released from dying cells. Cell death through necrosis induces inflammation, whereas apoptotic cell death provides an important signal for tolerance induction. High mobility group box 1 (HMGB1) is a DNA-binding nuclear protein, released actively following cytokine stimulation as well as passively during cell death; it is the prototypic damage-associated molecular pattern (DAMP) molecule and has been implicated in several inflammatory disorders. HMGB1 can associate with other molecules, including TLR ligands and cytokines, and activates cells through the differential engagement of multiple surface receptors including TLR2, TLR4, and RAGE. RAGE is a multiligand receptor that binds structurally diverse molecules, including not only HMGB1, but also S100 family members and amyloid-beta. RAGE activation has been implicated in sterile inflammation as well as in cancer, diabetes, and Alzheimer's disease. While HMGB1 through interactions with TLRs may also be important, this review focuses on the role of the HMGB1-RAGE axis in inflammation and cancer.
免疫系统的进化不仅是为了应对病原体，还为了应对来自死亡细胞释放的信号。坏死导致的细胞死亡会引发炎症，而凋亡细胞死亡则为诱导耐受提供了重要信号。高迁移率族蛋白 B1（HMGB1）是一种 DNA 结合核蛋白，在细胞因子刺激下主动释放，在细胞死亡时也会被动释放；它是典型的损伤相关分子模式（DAMP）分子，与多种炎症性疾病有关。HMGB1 可以与其他分子结合，包括 TLR 配体和细胞因子，并通过多种表面受体的不同结合来激活细胞，包括 TLR2、TLR4 和 RAGE。RAGE 是一种多配体受体，可与多种结构不同的分子结合，不仅包括 HMGB1，还包括 S100 家族成员和淀粉样β。RAGE 的激活不仅与无菌性炎症有关，还与癌症、糖尿病和阿尔茨海默病有关。虽然 HMGB1 通过与 TLR 的相互作用也可能很重要，但本篇综述重点关注 HMGB1-RAGE 轴在炎症和癌症中的作用。
