Hyperresponsive TH2 cells with enhanced nuclear factor-κB activation induce atopic dermatitis–like skin lesions in Nishiki-nezumi Cinnamon/Nagoya mice

Tenda, Yoshiyuki; Yamashita, Masakatsu; Kimura, Motoko; Hasegawa, Akira; Shimizu, Chiaki; Kitajima, Masayuki; Onodera, Atsushi; Suzuki, Akane; Seki, Nobuo; Nakayama, Toshinori

doi:10.1016/j.jaci.2006.05.024

Cited by 23 publications

(18 citation statements)

References 49 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…IL-4 is a crucial factor in IgE synthesis, and IL-5 is also a key factor in the activation and/or proliferation of eosinophils. In ex vivo analyses, the protein and mRNA levels of IL-4, IL-5, and IL-13 in spleen or lymph node cells are paralleled by AD-like skin legions in NC/ Nga mice (62,63). The intranasal administration of TiO 2 combined with allergen increase Th2 cytokines (IL-4, IL-5, and IL-13), and allergen-specific IgE and IgG1 levels in serum (28).…”

Section: Discussionmentioning

confidence: 97%

Titanium Dioxide Nanoparticles Aggravate Atopic Dermatitis-Like Skin Lesions in NC/Nga Mice

Yanagisawa

Takano

Inoue

et al. 2009

Exp Biol Med (Maywood)

View full text Add to dashboard Cite

Titanium dioxide (TiO(2)) nanoparticles are produced abundantly and used ubiquitously in various cosmetic products. However, it remains to be determined whether transdermal exposure to TiO(2) nanoparticles affects atopic dermatitis (AD), which has been increasing in developed countries. We investigated the effects of different sized TiO(2) nanoparticles on AD-like skin lesions induced to mite allergen in NC/Nga mice assumed to show skin barrier dysfunction/defect. Male mice were injected intradermally with TiO(2) nanoparticles of three sizes (15, 50, or 100 nm) and/or mite allergen into their right ears. We evaluated clinical scores, ear thickening, histological findings and the protein expression of T helper (Th) 1 and Th2 cytokines in the ear, and the levels of Ig and histamine in serum. TiO(2) nanoparticles aggravated AD-like skin lesions related to mite allergen in NC/ Nga mice. The enhancing effects are paralleled by the overproduction of IL-4 in the skin, the levels of total IgE and histamine in serum regarding the overall trend. In contrast, TiO(2) nanoparticles decreased the local expression of IFN-gamma in the presence of allergen. Additionally, TiO(2) nanoparticles alone significantly increased histamine levels in serum and IL-13 expression in the ear. However, different effects related to the size differences of TiO(2) nanoparticles were not observed. In conclusion, exposure to TiO(2) nanoparticles under skin barrier dysfunction/defect can exacerbate AD symptoms through Th2-biased immune responses. Furthermore, TiO(2) nanoparticles can play a significant role in the initiation and/or progression of skin diseases following the barrier dysfunction/defect by histamine release even in the absence of allergen.

show abstract

Section: Discussionmentioning

confidence: 97%

Titanium Dioxide Nanoparticles Aggravate Atopic Dermatitis-Like Skin Lesions in NC/Nga Mice

Yanagisawa

Takano

Inoue

et al. 2009

Exp Biol Med (Maywood)

View full text Add to dashboard Cite

show abstract

“…[66][67][68] Hyperresponsive T H 2 cells with enhanced nuclear factor-kB activation also contribute to enhanced skin inflammation in animal models of AD. 69 During the past year, there was considerable interest in the identification of IL-31 in human AD skin, because it is a novel T H 2-derived cytokine known to cause severe pruritus and eczema in animal models. Interestingly, IL-31 is primarily expressed in skin-homing T H 2, cells and its production is markedly increased by staphylococcal superantigens.…”

Section: Admentioning

confidence: 99%

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

Sicherer

Leung

2007

Journal of Allergy and Clinical Immunology

View full text Add to dashboard Cite

This review highlights some of the research advances in anaphylaxis and hypersensitivity reactions to foods, drugs, and insects and in allergic skin disease that were reported primarily in the Journal in 2006. Advances in diagnosis include identification of food proteins to which IgE binding is associated with severe reactions; elucidation of diagnostic relationships of skin prick test wheal size with outcomes of egg, tree nut, and sesame allergy; evaluation of the diagnostic utility of atopy patch testing for food; and the observation that yellow jacket sting outcomes are influenced by species. Mechanistic observations include the following: heating of birch pollen-related foods disrupts IgE binding but not T-cell epitopes; a simple imbalance of T(H)1/T(H)2 response does not explain variations in clinical expression of peanut allergy; and elucidation of the role of dendritic cells in drug hypersensitivity. With regard to treatment, a rapidly disintegrating epinephrine tablet showed promise for sublingual treatment of anaphylaxis, RNA interference techniques showed promise in creating lower-allergenic foods, and anti-IL-5 showed promise for treatment of eosinophilic esophagitis. Progress in our understanding of the immunology and the etiology of skin barrier dysfunction in atopic dermatitis has also been made. These observations will likely contribute toward optimizing management of these common allergic disorders.

show abstract

“…A variety of pro-inflammatory cytokines, including cyclooxygenase 2 (COX2) and prostaglandin E2 (PGE2), exert their biological effects through signaling cascades, leading to skin inflammation2223. Several investigations have shown activation of COX2/PGE2/nuclear factor kappaB (NFκB) signaling and down-regulation of filaggrin in the skin of patients with atopic dermatitis2425. However, the interactions between these two signaling pathways, and the way in which their effects coordinate to increase the risk of skin barrier dysfunction, remain largely unclear.…”

mentioning

confidence: 99%

Urban particulate matter down-regulates filaggrin via COX2 expression/PGE2 production leading to skin barrier dysfunction

Lee

Lin

et al. 2016

Sci Rep

136

152

View full text Add to dashboard Cite

We explored the regulation of filaggrin, cyclooxygenase 2 (COX2) and prostaglandin E2 (PGE2) expression induced by urban particulate matter (PM) in human keratinocytes. In addition, we investigated the signaling pathways involved in PM-induced effects on COX2/PGE2 and filaggrin. PMs induced increases in COX2 expression and PGE2 production, and decreased filaggrin expression. These effects were attenuated by pretreatment with COX2 inhibitor and PGE2 receptor antagonist, or after transfection with siRNAs of the aryl hydrocarbon receptor (AhR), gp91phox and p47phox. Furthermore, PM-induced generation of reactive oxygen species (ROS) and NADPH oxidase activity was attenuated by pretreatment with an AhR antagonist (AhRI) or antioxidants. Moreover, Nox-dependent ROS generation led to phosphorylation of ERK1/2, p38, and JNK, which then activated the downstream molecules NF-κB and AP-1, respectively. In vivo studies in PMs-treated mice showed that AhRI and apocynin (a Nox2 inhibitor) had anti-inflammatory effects by decreasing COX2 and increasing filaggrin expression. Our results reveal for the first time that PMs-induced ROS generation is mediated through the AhR/p47 phox/NADPH oxidase pathway, which in turn activates ERK1/2, p38/NF-κB and JNK/AP-1, and which ultimately induces COX2 expression and filaggrin downregulation. Up-regulated expression of COX2 and production of PGE2 may lead to impairment of skin barrier function.

show abstract

Hyperresponsive TH2 cells with enhanced nuclear factor-κB activation induce atopic dermatitis–like skin lesions in Nishiki-nezumi Cinnamon/Nagoya mice

Cited by 23 publications

References 49 publications

Titanium Dioxide Nanoparticles Aggravate Atopic Dermatitis-Like Skin Lesions in NC/Nga Mice

Titanium Dioxide Nanoparticles Aggravate Atopic Dermatitis-Like Skin Lesions in NC/Nga Mice

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

Urban particulate matter down-regulates filaggrin via COX2 expression/PGE2 production leading to skin barrier dysfunction

Contact Info

Product

Resources

About