DMF, but not other fumarates, inhibits NF-κB activity in vitro in an Nrf2-independent manner

被引：146

作者：

Gillard, Geoffrey O. ^{[1
]}

Collette, Brian ^{[1
]}

Anderson, John ^{[1
]}

Chao, Jianhua ^{[1
]}

Scannevin, Robert H. ^{[1
]}

Huss, David J. ^{[1
]}

Fontenot, Jason D. ^{[1
]}

机构：

[1] Biogen Inc, Cambridge, MA 02142 USA

来源：

JOURNAL OF NEUROIMMUNOLOGY | 2015年 / 283卷

关键词：

Dimethyl fumarate (DMF); Monomethyl fumarate (MMF); Monoethyl fumarate (MEF); Nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kappa B); Nuclear factor (elythroid-derived 2)-like 2 (Nrf2); Cytokine; FUMARIC-ACID ESTERS; REMITTING MULTIPLE-SCLEROSIS; PLACEBO-CONTROLLED PHASE-3; HUMAN ENDOTHELIAL-CELLS; DIMETHYL FUMARATE; NICOTINIC-ACID; NUCLEAR-FACTOR; ANTIOXIDANT RESPONSE; OXIDATIVE STRESS; DENDRITIC CELLS;

D O I：

10.1016/j.jneuroim.2015.04.006

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

Fumarate-containing pharmaceuticals are potent therapeutic agents that influence multiple cellular pathways. Despite proven clinical efficacy, there is a significant lack of data that directly defines the molecular mechanisms of action of related, yet distinct fumarate compounds. We systematically compared the impact of dimethyl fumarate (DMF), monomethyl fumarate (MMF) and a mixture of monoethyl fumarate salts (Ca++, Mg++, Zn++; MEF) on defined cellular responses. We demonstrate that DMF inhibited NF-kappa B-driven cytokine production and nuclear translocation of p65 and p52 in an Nrf2-independent manner. Equivalent doses of MMF and MEF did not affect NF-kappa B signaling. These results highlight a key difference in the biological impact of related, yet distinct fumarate compounds. (C) 2015 The Authors. Published by Elsevier B.V.

引用

页码：74 / 85

页数：12

共 73 条

[71] Dimethylfumarate inhibits microglial and astrocytic inflammation by suppressing the synthesis of nitric oxide, IL-1β, TNF-α and IL-6 in an in-vitro model of brain inflammation [J].