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KMID : 0624620160490040214
BMB Reports
2016 Volume.49 No. 4 p.214 ~ p.219
Anti-septic effects of dabrafenib on HMGB1-mediated inflammatory responses
Jung Byeong-Jin

Kang Hye-Jin
Lee Won-Hwa
Noh Hyun-Jin
Kim You-Sun
Han Min-Su
Baek Moon-Chang
Kim Jae-Hong
Bae Jong-Sup
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.
KEYWORD
Barrier integrity, Dabrafenib, HMGB1, Sepsis
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