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

Abstract EN

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.