Upregulation of miR-18a-5p contributes to epidermal necrolysis in severe drug eruptions

Ichihara, Asako; Wang, Zhongzhi; Jinnin, Masatoshi; Izuno, Yuki; Shimozono, Naoki; Yamane, Keitaro; Fujisawa, Akihiko; Moriya, Chikako; Fukushima, Satoshi; Inoue, Yoshio; Ihn, Hironobu

doi:10.1016/j.jaci.2013.09.019

Cited by 50 publications

(53 citation statements)

References 39 publications

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“…Insight into the mechanism of keratinocyte apoptosis in patients with toxic epidermal necrolysis (TEN) was noted in a study of microRNAs extracted from tissues and sera of patients and through supporting in vitro studies. 92 A specific upregulated microRNA, miR-18a-5p, was detected in lesions from patients with TEN and was distinct from other types of rashes tested, and a dose response was noted for milder drug eruptions on the spectrum of TEN. Additional studies noted that a target of miR-18a-5p is the apoptosis gene BCL2L10, further indicating pathologic significance.…”

Section: Drug Allergymentioning

confidence: 93%

Advances in allergic skin disease, anaphylaxis, and hypersensitivity reactions to foods, drugs, and insects in 2014

Sicherer

Leung

2015

Journal of Allergy and Clinical Immunology

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This review highlights some of the research advances in anaphylaxis; hypersensitivity reactions to foods, drugs, and insects; and allergic skin diseases that were reported in the Journal in 2014. Studies on food allergy suggest worrisomely high rates of peanut allergy and food-induced anaphylaxis-related hospitalizations. Evidence is mounting to support the theory that environmental exposure to peanut, such as in house dust, especially with an impaired skin barrier attributed to atopic dermatitis (AD) and loss of function mutations in the filaggrin gene, is a risk factor for sensitization and allergy. Diagnostic tests are improving, with early studies suggesting the possibility of developing novel cellular tests with increased diagnostic utility. Treatment trials continue to show the promise and limitations of oral immunotherapy, and mechanistic studies are elucidating pathways that might define the degree of efficacy of this treatment. Studies have also provided insights into the prevalence and characteristics of anaphylaxis and insect venom allergy, such as suggesting that baseline platelet-activating factor acetylhydrolase activity levels are related to the severity of reactions. Advances in drug allergy include identification of HLA associations for penicillin allergy and a microRNA biomarker/mechanism for toxic epidermal necrolysis. Research identifying critical events leading to skin barrier dysfunction and the polarized immune pathways that drive AD have led to new therapeutic approaches in the prevention and management of AD.

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Section: Drug Allergymentioning

confidence: 93%

Advances in allergic skin disease, anaphylaxis, and hypersensitivity reactions to foods, drugs, and insects in 2014

Sicherer

Leung

2015

Journal of Allergy and Clinical Immunology

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“…Ultimately, fulminant keratinocyte cell death and extensive epidermal detachment represent the effector phase and the final consequence of the hypersensitivity response. Cytotoxic immune cells and/or soluble factors such as granulysin, CD95L, annexin A1, and micro RNA 18a-5p regulation have been suggested as causing keratinocyte death (Viard et al, 1998;Chung et al, 2008;Chung and Hung, 2012;Ichihara et al, 2014;Saito et al, 2014). Interestingly, both of the major forms of cell death, apoptosis and necrosis, appear to have roles.…”

mentioning

confidence: 99%

“…Activated RIPK3 gains the ability to phosphorylate and activate mixed lineage kinase domain-like protein(MLKL; Murphy et al, 2013). Phosphorylated MLKL molecules form homooligomers, which form pores and disrupt membrane integrity, finally resulting in cell death (Wang et al, 2014) The core molecular complex of RIPK1 and RIPK3 has long been recognized as the necrosome (Vanden Berghe et al, 2014). How to retain the proper quality and quantity of cell death in keratinocytes during the progression of TEN is thus an important question.…”

mentioning

confidence: 99%

RIPping the Skin Apart: Necroptosis Signaling in Toxic Epidermal Necrolysis

Panayotova-Dimitrova

Feoktistova

Leverkus

2015

Journal of Investigative Dermatology

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Toxic epidermal necrolysis (TEN) is a rare but potentially fatal drug hypersensitivity reaction. Although a number of pathophysiological hints have been identified over the past decade, details of the effector mechanisms within the skin remain obscure. A novel study by Kim et al. now sheds light on its pathophysiology. The investigators demonstrate convincingly that receptor-interacting kinase 3 (RIPK3) levels are upregulated substantially in the lesional skin of patients with TEN and that this is followed by the generation of reactive oxygen species, activation of mixed lineage kinase-like protein, and subsequent necroptotic cell death of keratinocytes. These data suggest that therapies that interfere with RIPK3 activation and necroptosis induction could benefit patients with TEN.

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“…MicroRNA expression profile were downloaded from the inclusive miRNA expression profile of patients skin suffering from TEN using an array comprising of 372 miRNAs; Ichihara et al article's Online Repository at www.jacionline.org [13]. The samples were achieved from eight TEN patients, ten SJS patients with and 22 healthy volunteers.…”

Section: Micrornas Array: Differentially Expressed In Scarmentioning

confidence: 99%

MicroRNA and gene signature of severe cutaneous drug hypersensitivity reactions reveal the role of miR-483- 5p/miR-28-5p in inflammation by targeting Granulysin gene

Elbakkoush¹,

Khaleel²,

Liu³

2017

Trop. J. Pharm Res

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Upregulation of miR-18a-5p contributes to epidermal necrolysis in severe drug eruptions

Cited by 50 publications

References 39 publications

Advances in allergic skin disease, anaphylaxis, and hypersensitivity reactions to foods, drugs, and insects in 2014

Advances in allergic skin disease, anaphylaxis, and hypersensitivity reactions to foods, drugs, and insects in 2014

RIPping the Skin Apart: Necroptosis Signaling in Toxic Epidermal Necrolysis

MicroRNA and gene signature of severe cutaneous drug hypersensitivity reactions reveal the role of miR-483- 5p/miR-28-5p in inflammation by targeting Granulysin gene

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