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BMB Rep. 2016 Apr;49(4):214-9.

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

Author information

1
College of Pharmacy, CMRI, Research Institute of Pharmaceutical Sciences, Kyungpook National University, Daegu 41566, Korea.
2
College of Pharmacy, CMRI, Research Institute of Pharmaceutical Sciences, Kyungpook National University, Daegu 41566; Department of Biochemistry and Cell Biology, BK21 Plus KNU Biomedical Convergence Program, School of Medicine, Kyungpook National University, Daegu 41944, Korea.
3
Department of Biochemistry and Department of Biomedical Sciences, Ajou University School of Medicine, Suwon 16499, Korea.
4
Laboratory for Arthritis and Bone Biology, Fatima Research Institute, Fatima Hospital, Daegu 41199, Korea.
5
Department of Molecular Medicine, CMRI, School of Medicine, Kyungpook National University, Daegu 41944, Korea.
6
Department of Biochemistry, School of Medicine, Gachon University, Incheon 21999, Korea.

Abstract

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. [BMB Reports 2016; 49(4): 214-219].

PMID:
26592934
PMCID:
PMC4915240
[Indexed for MEDLINE]
Free PMC Article

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