Anti-septic effects of dabrafenib on HMGB1-mediated inflammatory responses

作者：Jung Byeongjin; Kang Hyejin; Lee Wonhwa; Noh Hyun Jin; Kim You Sun; Han Min Su; Baek Moon Chang^*; Kim Jaehong^*; Bae Jong Sup^*

来源：BMB Reports, 2016, 49(4): 214-219.

DOI：10.5483/BMBRep.2016.49.4.220

• Barrier integrity
• Dabrafenib
• HMGB1
• Sepsis

A nucleosomal protein, high mobility group box 1 (HMGB1) is known to be a late mediator of sepsis. Dabrafenib is a B-Raf inhibitor and initially used for the treatment of metastatic melanoma therapy. Inhibition of HMGB1 and renewal of vascular integrity is appearing as an engaging therapeutic strategy in the administration of severe sepsis or septic shock. Here, we examined the effects of dabrafenib (DAB) on the modulation of HMGB1-mediated septic responses. DAB inhibited the release of HMGB1 and downregulated HMGB1-dependent inflammatory responses by enhancing the expressions of cell adhesion molecules (CAMs) in human endothelial cells. In addition, treatment with DAB inhibited the HMGB1 secretion by CLP and sepsis-related mortality and pulmonary injury. This study demonstrated that DAB could be alternative therapeutic options for sepsis or septic shock via the inhibition of the HMGB1 signaling pathway.

• 出版日期2016-4