The Anti-Inflammatory Activity of HMGB1 A Box Is Enhanced When Fused with C-Terminal Acidic Tail

• Main Authors: Wei Gong, Yingru Zheng, Fan Chao, Yuan Li, Zhizhen Xu, Gang Huang, Xiang Gao, Song Li, Fengtian He
• Format: Article
• Language: English
• Published: Hindawi Limited 2010-01-01
• Series: Journal of Biomedicine and Biotechnology
• Online Access: http://dx.doi.org/10.1155/2010/915234

HMGB1, composed of the A box, B box, and C tail domains, is a critical proinflammatory cytokine involved in diverse inflammatory diseases. The B box mediates proinflammatory activity, while the A box alone acts as a specific antagonist of HMGB1. The C tail contributes to the spatial structure of A box and regulates HMGB1 DNA binding specificity. It is unknown whether the C tail can enhance the anti-inflammatory effect of A box. In this study, we generated fusion proteins consisting of the A box and C tail, in which the B box was deleted and the A box and C tail were linked either directly or by the flexible linker sequence (Gly4Ser)3. In vitro and in vivo experiments showed that the two fusion proteins had a higher anti-inflammatory activity compared to the A box alone. This suggests that the fused C tail enhances the anti-inflammatory effect of the A box.