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Anti-septic effects of dabrafenib on HMGB1-mediated inflammatory responses
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  • Journal title : BMB Reports
  • Volume 49, Issue 4,  2016, pp.214-219
  • Publisher : Korean Society for Biochemistry and Molecular Biology
  • DOI : 10.5483/BMBRep.2016.49.4.220
 Title & Authors
Anti-septic effects of dabrafenib on HMGB1-mediated inflammatory responses
Jung, Byeongjin; Kang, Hyejin; Lee, Wonhwa; Noh, Hyun Jin; Kim, You-Sun; Han, Min-Su; Baek, Moon-Chang; Kim, Jaehong; Bae, Jong-Sup;
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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.
Barrier integrity;Dabrafenib;HMGB1;Sepsis;
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Russell JA (2006) Management of sepsis. N Engl J Med 355, 1699-1713 crossref(new window)

Andreu Ballester JC, Ballester F, Gonzalez Sanchez A, Almela Quilis A, Colomer Rubio E and Penarroja Otero C (2008) Epidemiology of sepsis in the Valencian Community (Spain), 1995-2004. Infect Control Hosp Epidemiol 29, 630-634 crossref(new window)

Angus DC and Wax RS (2001) Epidemiology of sepsis: an update. Crit Care Med 29, S109-116 crossref(new window)

Bernard GR, Vincent JL, Laterre PF et al (2001) Efficacy and safety of recombinant human activated protein C for severe sepsis. N Engl J Med 344, 699-709 crossref(new window)

Thachil J, Toh CH, Levi M and Watson HG (2012) The withdrawal of Activated Protein C from the use in patients with severe sepsis and DIC [Amendment to the BCSH guideline on disseminated intravascular coagulation]. Br J Haematol 157, 493-494 crossref(new window)

Bhatia M, He M, Zhang H and Moochhala S (2009) Sepsis as a model of SIRS. Front Biosci 14, 4703-4711 crossref(new window)

Tracey KJ, Fong Y, Hesse DG et al (1987) Anti-cachectin/TNF monoclonal antibodies prevent septic shock during lethal bacteraemia. Nature 330, 662-664 crossref(new window)

Wang H, Yang H, Czura CJ, Sama AE and Tracey KJ (2001) HMGB1 as a late mediator of lethal systemic inflammation. Am J Respir Crit Care Med 164, 1768-1773 crossref(new window)

Bianchi ME and Agresti A (2005) HMG proteins: dynamic players in gene regulation and differentiation. Curr Opin Genet Dev 15, 496-506 crossref(new window)

Ulloa L and Tracey KJ (2005) The "cytokine profile": a code for sepsis. Trends Mol Med 11, 56-63 crossref(new window)

Bae JS and Rezaie AR (2011) Activated protein C inhibits high mobility group box 1 signaling in endothelial cells. Blood 118, 3952-3959 crossref(new window)

Sunden-Cullberg J, Norrby-Teglund A, Rouhiainen A et al (2005) Persistent elevation of high mobility group box-1 protein (HMGB1) in patients with severe sepsis and septic shock. Crit Care Med 33, 564-573 crossref(new window)

Gibot S, Massin F, Cravoisy A et al (2007) High-mobility group box 1 protein plasma concentrations during septic shock. Intensive Care Med 33, 1347-1353 crossref(new window)

Bae JS (2012) Role of high mobility group box 1 in inflammatory disease: Focus on sepsis. Arch Pharm Res 35, 1511-1523 crossref(new window)

Li JX, Feng JM, Wang Y et al (2014) The B-Raf(V600E) inhibitor dabrafenib selectively inhibits RIP3 and alleviates acetaminophen-induced liver injury. Cell Death Dis 5, e1278 crossref(new window)

Padhy BM and Gupta YK (2011) Drug repositioning: re-investigating existing drugs for new therapeutic indications. J Postgrad Med 57, 153-160 crossref(new window)

Liu X, Zhu F, Ma XH et al (2013) Predicting targeted polypharmacology for drug repositioning and multi- target drug discovery. Curr Med Chem 20, 1646-1661 crossref(new window)

O'Connor KA and Roth BL (2005) Finding new tricks for old drugs: an efficient route for public-sector drug discovery. Nat Rev Drug Discov 4, 1005-1014 crossref(new window)

van Beijnum JR, Buurman WA and Griffioen AW (2008) Convergence and amplification of toll-like receptor (TLR) and receptor for advanced glycation end products (RAGE) signaling pathways via high mobility group B1 (HMGB1). Angiogenesis 11, 91-99 crossref(new window)

El Gazzar M (2007) HMGB1 modulates inflammatory responses in LPS-activated macrophages. Inflamm Res 56, 162-167 crossref(new window)

Mullins GE, Sunden-Cullberg J, Johansson AS et al (2004) Activation of human umbilical vein endothelial cells leads to relocation and release of high-mobility group box chromosomal protein 1. Scand J Immunol 60, 566-573 crossref(new window)

Czura CJ, Yang H and Tracey KJ (2003) High mobility group box-1 as a therapeutic target downstream of tumor necrosis factor. J Infect Dis 187 Suppl 2, S391-396 crossref(new window)

Diehl KH, Hull R, Morton D et al (2001) A good practice guide to the administration of substances and removal of blood, including routes and volumes. J Appl Toxicol 21, 15-23 crossref(new window)

Lee W, Ku SK, Lee YM and Bae JS (2014) Anti-septic effects of glyceollins in HMGB1-induced inflammatory responses in vitro and in vivo. Food Chem Toxicol 63, 1-8 crossref(new window)

Qin YH, Dai SM, Tang GS et al (2009) HMGB1 enhances the proinflammatory activity of lipopolysaccharide by promoting the phosphorylation of MAPK p38 through receptor for advanced glycation end products. J Immunol 183, 6244-6250 crossref(new window)

Sun C, Liang C, Ren Y et al (2009) Advanced glycation end products depress function of endothelial progenitor cells via p38 and ERK 1/2 mitogen-activated protein kinase pathways. Basic Res Cardiol 104, 42-49 crossref(new window)

Palumbo R, Galvez BG, Pusterla T et al (2007) Cells migrating to sites of tissue damage in response to the danger signal HMGB1 require NF-kappaB activation. J Cell Biol 179, 33-40 crossref(new window)

Luo Y, Li SJ, Yang J, Qiu YZ and Chen FP (2013) HMGB1 induces an inflammatory response in endothelial cells via the RAGE-dependent endoplasmic reticulum stress pathway. Biochem Biophys Res Commun 438, 732-738 crossref(new window)

Erlandsson Harris H and Andersson U (2004) Mini-review: The nuclear protein HMGB1 as a proinflammatory mediator. Eur J Immunol 34, 1503-1512 crossref(new window)

Park JS, Gamboni-Robertson F, He Q et al (2006) High mobility group box 1 protein interacts with multiple Tolllike receptors. Am J Physiol Cell Physiol 290, C917-924 crossref(new window)

Yang EJ, Ku SK, Lee W et al (2013) Barrier protective effects of rosmarinic acid on HMGB1-induced inflammatory responses in vitro and in vivo. J Cell Physiol 228, 975-982 crossref(new window)

Astiz ME and Rackow EC (1998) Septic shock. Lancet 351, 1501-1505 crossref(new window)