BMB Rep. 2016; 49(4): 214-219  
Anti-septic effects of dabrafenib on HMGB1-mediated inflammatory responses
Byeongjin Jung1,#, Hyejin Kang1,#, Wonhwa Lee1,2, Hyun Jin Noh3, You-Sun Kim3, Min-Su Han4, Moon-Chang Baek5,*, Jaehong Kim6,* & Jong-Sup Bae1,*
1College of Pharmacy, CMRI, Research Institute of Pharmaceutical Sciences, Kyungpook National University, Daegu 41566, 2Department of Biochemistry and Cell Biology, BK21 Plus KNU Biomedical Convergence Program, School of Medicine, Kyungpook National University, Daegu 41944, 3Department of Biochemistry and Department of Biomedical Sciences, Ajou University School of Medicine, Suwon 16499, 4Laboratory for Arthritis and Bone Biology, Fatima Research Institute, Fatima Hospital, Daegu 41199, 5Department of Molecular Medicine, CMRI, School of Medicine, Kyungpook National University, Daegu 41944, 6Department of Biochemistry, School of Medicine, Gachon University, Incheon 21999, Korea
Correspondence to: Moon-Chang Baek, Tel: +82-53-420-4948; Fax: +82-53-420-4944; E-mail: mcbaek@knu.ac.kr, Jaehong Kim, Tel: +82-32-899-6341; Fax: +82-32-899-6039; E-mail: geretics@gachon.ac.kr, Jong-Sup Bae, Tel: +82-53-950-8570; Fax: +82-53-950-8557; E-mail: baejs@knu.ac.kr
Received: October 24, 2015; Revised: November 6, 2015; Accepted: November 16, 2015; Published online: April 30, 2016.
© Korean Society for Biochemistry and Molecular Biology. All rights reserved.

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.
Keywords: Barrier integrity, Dabrafenib, HMGB1, Sepsis


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