Department of Dermatology and Allergy, University Hospital, LMU Munich, Frauenlobstrasse, Munich, Germany.
J Dermatol Sci. 2022 Aug;107(2):58-64. doi: 10.1016/j.jdermsci.2022.07.005. Epub 2022 Jul 13.
High-mobility group box 1 protein (HMGB1) is a highly abundant, non-histone nuclear protein that can serve as an alarmin to promote the pathogenesis of inflammatory diseases. In response to various stimuli, HMGB1 can translocate from the nucleus to the cytoplasm as well as the extracellular space through passive or active release, accompanied with different post-translational modifications. Depending on the redox state of three cysteine residues, HMGB1 determines its activity to induce cytokine production or tissue repair through binding with several different receptors. In addition, HMGB1 can form immunostimulatory complexes with cytokines and other endogenous/exogenous molecules and synergistically enhance their biological effect. Cell death is an important source of HMGB1 and major cell death forms such as apoptosis, necrosis and pyroptosis can modulate the redox state of HMGB1. In various human skin diseases as well as animal models, HMGB1 levels in cytoplasm, tissue and blood are increased and blockade of HMGB1 attenuates disease severity in animal models. These findings indicate that HMGB1 can serve as a unique biomarker as well as a target of new therapy in many inflammatory skin diseases.
高迁移率族蛋白 B1（HMGB1）是一种含量丰富的非组蛋白核蛋白，可作为警报素促进炎症性疾病的发病机制。HMGB1 可以在各种刺激下通过被动或主动释放从细胞核易位到细胞质和细胞外空间，并伴有不同的翻译后修饰。HMGB1 通过与几种不同的受体结合，根据三个半胱氨酸残基的氧化还原状态，决定其诱导细胞因子产生或组织修复的活性。此外，HMGB1 可以与细胞因子和其他内源性/外源性分子形成免疫刺激复合物，并协同增强它们的生物学效应。细胞死亡是 HMGB1 的重要来源，凋亡、坏死和细胞焦亡等主要细胞死亡形式可以调节 HMGB1 的氧化还原状态。在各种人类皮肤病和动物模型中，细胞质、组织和血液中的 HMGB1 水平增加，阻断 HMGB1 可减轻动物模型中的疾病严重程度。这些发现表明，HMGB1 可以作为许多炎症性皮肤病的独特生物标志物和新治疗靶点。
