The antipsoriatic drug dimethylfumarate strongly suppresses chemokine production in human keratinocytes and peripheral blood mononuclear cells

Stoof, T.J.; Flier, Jacoba; Sampat, S.; Nieboer, C.; Tensen, Cornelis P.; Boorsma, D. M.

doi:10.1046/j.1365-2133.2001.04220.x

Cited by 108 publications

(92 citation statements)

References 31 publications

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“…MIF (3) in (1,5,7,9,11) or siControl ? MIF (4) in (2,6,8,10,12). Results in vehicle (1, 2), MSK1 siRNA ?…”

Section: Discussionmentioning

confidence: 99%

“…Dimethylfumarate (DMF) has recently been shown to be the most effective component in the mixture of different FAEs [2][3][4]. Lately, we showed that DMF, in cultured human keratinocytes, inhibits interleukin (IL)-1b induced phosphorylation of mitogen-and stress-activated protein kinase 1 (MSK1) (Ser376), the nuclear translocation of nuclear factor (NF)-jB and the phosphorylation of NF-jB p65 (Ser276), cAMP-responsive element-binding protein (CREB) (Ser133) and activator transcription factor 1 (ATF1) which are downstream from MSK1 [5].…”

Section: Introductionmentioning

confidence: 99%

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Dimethylfumarate inhibits MIF-induced proliferation of keratinocytes by inhibiting MSK1 and RSK1 activation and by inducing nuclear p-c-Jun (S63) and p-p53 (S15) expression

et al. 2011

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“…MIF (3) in (1,5,7,9,11) or siControl ? MIF (4) in (2,6,8,10,12). Results in vehicle (1, 2), MSK1 siRNA ?…”

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Dimethylfumarate inhibits MIF-induced proliferation of keratinocytes by inhibiting MSK1 and RSK1 activation and by inducing nuclear p-c-Jun (S63) and p-p53 (S15) expression

et al. 2011

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“…In human keratinocytes and peripheral blood mononuclear cells stimulated with IFN-g or LPS, dimethyl fumarate (Fig. 9) inhibits the production of chemokines that may be critically involved in the development and persistance of psoriatic lesions (426). In patients with relapsing-remitting multiple sclerosis, dimethyl fumarate reduced the formation of new inflammatory lesions in both a pilot study (392) and a multicenter, randomized, double-blind, placebo-controlled, dose-escalation, Phase IIb study (224).…”

Section: Dimethyl Fumaratementioning

confidence: 99%

Cellular Stress Responses, The Hormesis Paradigm, and Vitagenes: Novel Targets for Therapeutic Intervention in Neurodegenerative Disorders

Calabrese

Cornelius

Dinkova‐Kostova

et al. 2010

Antioxidants & Redox Signaling

717

573

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Despite the capacity of chaperones and other homeostatic components to restore folding equilibrium, cells appear poorly adapted for chronic oxidative stress that increases in cancer and in metabolic and neurodegenerative diseases. Modulation of endogenous cellular defense mechanisms represents an innovative approach to therapeutic intervention in diseases causing chronic tissue damage, such as in neurodegeneration. This article introduces the concept of hormesis and its applications to the field of neuroprotection. It is argued that the hormetic dose response provides the central underpinning of neuroprotective responses, providing a framework for explaining the common quantitative features of their dose-response relationships, their mechanistic foundations, and their relationship to the concept of biological plasticity, as well as providing a key insight for improving the accuracy of the therapeutic dose of pharmaceutical agents within the highly heterogeneous human population. This article describes in mechanistic detail how hormetic dose responses are mediated for endogenous cellular defense pathways, including sirtuin and Nrf2 and related pathways that integrate adaptive stress responses in the prevention of neurodegenerative diseases. Particular attention is given to the emerging role of nitric oxide, carbon monoxide, and hydrogen sulfide gases in hormetic-based neuroprotection and their relationship to membrane radical dynamics and mitochondrial redox signaling.

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“…Showing a prevailing effect on Th2-cellpromoting, so called type II, dendritic cells, these studies provide further insights on the cascades of cellular events that may follow exposure to DMF [Ghoreschi et al 2011]. Beyond its effects on T-cells and dendritic cells, DMF may also target several other immunologically active cell types, namely neutrophils, macrophages, monocytes, endothelial cells or keratinocytes [Asadullah et al 1997;Loewe et al 2002;Nibbering et al 1993;Ockenfels et al 1998;Schilling et al 2006;Sebok et al 1998;Stoof et al 2001]. …”

Section: Dimethyl Fumarate: Pharmacokinetic Datamentioning

confidence: 99%

Dimethyl fumarate in multiple sclerosis: latest developments, evidence and place in therapy

Linker

Haghikia

2016

Therapeutic Advances in Chronic Disease

114

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Dimethyl fumarate (DMF) is one of the newer additions to the armamentarium of potent immunomodulators for the treatment of relapsing-remitting multiple sclerosis (RRMS). After more than 2 years of real-world experience and more than 190,000 patients currently treated with DMF worldwide, it is a good timepoint to review the experience gathered so far and to re-evaluate the potential of this first-line oral multiple sclerosis (MS) drug. Post-hoc analyses of clinical and magnetic resonance imaging (MRI) data, some comprising more than 6 years of drug exposure including patients from the clinical trials, and the overall notion in clinical practice widely confirm the good efficacy of DMF in RRMS. Despite an overall good safety profile, it became also clear that the necessary clinical vigilance while using DMF may not be neglected. So far, four reported cases of progressive multifocal leukoencephalopathy (PML), a towering shadow over many MS therapies, warrant proper attention in newly-updated risk management plans. This review recapitulates efficacy and safety aspects of DMF therapy in relation to reported data from the pivotal clinical trials. In addition, we summarize recent insights into DMF mechanisms of action drawn from the field of basic research which may have important implications for clinical practice.

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The antipsoriatic drug dimethylfumarate strongly suppresses chemokine production in human keratinocytes and peripheral blood mononuclear cells

Abstract: These results show the ability of DMF to inhibit the production of chemokines that may be critically involved in the development and perpetuation of psoriatic lesions. This might explain, at least in part, the beneficial effects of treatment with fumaric acid esters in psoriasis patients.

Cited by 108 publications

References 31 publications

Dimethylfumarate inhibits MIF-induced proliferation of keratinocytes by inhibiting MSK1 and RSK1 activation and by inducing nuclear p-c-Jun (S63) and p-p53 (S15) expression

Dimethylfumarate inhibits MIF-induced proliferation of keratinocytes by inhibiting MSK1 and RSK1 activation and by inducing nuclear p-c-Jun (S63) and p-p53 (S15) expression

Cellular Stress Responses, The Hormesis Paradigm, and Vitagenes: Novel Targets for Therapeutic Intervention in Neurodegenerative Disorders

Dimethyl fumarate in multiple sclerosis: latest developments, evidence and place in therapy

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