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Yang, De; Chen, Qian; Yang, Huan; Tracey, Kevin J.; Bustin, Michael; Oppenheim, Joost J.
Journal of leukocyte biology, January 2007, Volume: 81, Issue: 1Journal Article
High mobility group box‐1 (HMGB1) protein is a nonhistone, DNA‐binding protein that plays a critical role in regulating gene transcription. Recently, HMGB1 has also been shown to act as a late mediator of endotoxic shock and to exert a variety of proinflammatory, extracellular activities. Here, we report that HMGB1 simultaneously acts as a chemoattractant and activator of dendritic cells (DCs). HMGB1 induced the migration of monocyte‐derived, immature DCs (Mo‐iDCs) but not mature DCs. The chemotactic effect of HMGB1 on iDCs was pertussis toxin‐inhibitable and also inhibited by antibody against the receptor of advanced glycation end products (RAGE), suggesting that HMGB1 chemoattraction of iDCs is mediated by RAGE in a Gi protein‐dependent manner. In addition, HMGB1 treatment of Mo‐iDCs up‐regulated DC surface markers (CD80, CD83, CD86, and HLA‐A, B,C), enhanced DC production of cytokines (IL‐6, CXCL8, IL‐12p70, and TNF‐α), switched DC chemokine responsiveness from CCL5‐sensitive to CCL21‐sensitive, and acquired the capacity to stimulate allogeneic T cell proliferation. Based on its dual DC‐attracting and ‐activating activities as well as its reported capacity to promote an antigen‐specific immune response, we consider HMGB1 to have the properties of an immune alarmin.
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