The Expression and Regulation of Interleukin-33 in Human Epidermal Keratinocytes: A New Mediator of Atopic Dermatitis and Its Possible Signaling Pathway

2016 ◽  
Vol 36 (9) ◽  
pp. 552-562 ◽  
Author(s):  
Hong-Yang Du ◽  
Hai-Yan Fu ◽  
Dong-Ning Li ◽  
Yuan Qiao ◽  
Qiao-Wei Wang ◽  
...  
Keyword(s):  
Atopic Dermatitis ◽  
Signaling Pathway ◽  
Epidermal Keratinocytes ◽  
Human Epidermal Keratinocytes ◽  
Interleukin 33

scholarly journals LIGHT–HVEM signaling in keratinocytes controls development of dermatitis

2018 ◽  
Vol 215 (2) ◽  
pp. 415-422 ◽  
Author(s):  
Rana Herro ◽  
Jr-Wen Shui ◽  
Sonja Zahner ◽  
Daniel Sidler ◽  
Yuko Kawakami ◽  
...  
Keyword(s):  
Atopic Dermatitis ◽  
Skin Diseases ◽  
Disease Onset ◽  
Epidermal Keratinocytes ◽  
Matricellular Protein ◽  
Central Feature ◽  
Human Epidermal Keratinocytes ◽  
Conditional Deletion ◽  
Tnf Superfamily ◽  
Dermal Collagen

Dermatitis is often associated with an allergic reaction characterized by excessive type 2 responses leading to epidermal acanthosis, hyperkeratosis, and dermal inflammation. Although factors like IL-4, IL-13, and thymic stromal lymphopoietin (TSLP) are thought to be instrumental for the development of this type of skin disorder, other cytokines may be critical. Here, we show that the tumor necrosis factor (TNF) superfamily protein LIGHT (homologous to lymphotoxin, exhibits inducible expression, and competes with HSV glycoprotein D for binding to HVEM, a receptor expressed on T lymphocytes) is required for experimental atopic dermatitis, and LIGHT directly controls keratinocyte hyperplasia, and production of periostin, a matricellular protein that contributes to the clinical features of atopic dermatitis as well as other skin diseases such as scleroderma. Mice with a conditional deletion of the LIGHT receptor HVEM (herpesvirus entry mediator) in keratinocytes phenocopied LIGHT-deficient mice in exhibiting reduced epidermal thickening and dermal collagen deposition in a model of atopic dermatitis driven by house dust mite allergen. LIGHT signaling through HVEM in human epidermal keratinocytes directly induced proliferation and periostin expression, and both keratinocyte-specific deletion of HVEM or antibody blocking of LIGHT–HVEM interactions after disease onset prevented expression of periostin and limited atopic dermatitis symptoms. Developing reagents that neutralize LIGHT–HVEM signaling might be useful for therapeutic intervention in skin diseases where periostin is a central feature.

scholarly journals Epidermal Growth Factor Relieves Inflammatory Signals inStaphylococcus aureus-Treated Human Epidermal Keratinocytes and Atopic Dermatitis-Like Skin Lesions in Nc/Nga Mice

2018 ◽  
Vol 2018 ◽  
pp. 1-9 ◽  
Author(s):  
Sun Young Choi ◽  
You Jin Lee ◽  
Ji Min Kim ◽  
Hyun Ji Kang ◽  
Sang Hyun Cho ◽  
...  
Keyword(s):  
Atopic Dermatitis ◽  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Opposite Effect ◽  
Egf Receptor ◽  
Skin Lesions ◽  
Epidermal Keratinocytes ◽  
Human Epidermal Keratinocytes ◽  
Epidermal Growth

Atopic dermatitis (AD) is a chronic inflammatory skin disease with a defective immunologic barrier, which is aggravated byStaphylococcus aureus (S. aureus). Epidermal growth factor (EGF) suppresses inflammation and EGF receptor inhibitors increasedS. aureuscolonization. Thus, we investigated the potential roles of EGF in AD, which is often aggravated byS. aureus. We determined how EGF affects the expression of inflammatory cytokines and antimicrobial peptides (AMPs) in human epidermal keratinocytes (HEKs) treated with heat-inactivatedS. aureus(HKSA)in vitroand 2,4-dinitrochlorobenzene-induced AD-like skin lesions in Nc/Nga mice. HKSA increased IL-6 and NFκB expression; EGF treatment had the opposite effect. EGF increased humanβdefensin-2 expression in HEKs and murineβdefensin-3 in mice. In mice, both EGF and pimecrolimus groups showed less erythema with significantly reduced inflammation and decreased expression of thymic stromal lymphopoietin. EGF relievedS. aureus-induced inflammation and AD-like skin lesions in Nc/Nga mice. Therefore, EGF could be a potential topical treatment for AD.

scholarly journals MAPK pathway involved in epidermal terminal differentiation of normal human epidermal keratinocytes

Open Medicine ◽  
2018 ◽  
Vol 13 (1) ◽  
pp. 189-195 ◽  
Author(s):  
Xianguang Meng ◽  
Liyun Qiu ◽  
Haiyan Song ◽  
Ningning Dang
Keyword(s):  
Signaling Pathway ◽  
Mapk Pathway ◽  
Terminal Differentiation ◽  
Epidermal Keratinocytes ◽  
Human Epidermal Keratinocytes ◽  
Mapk Pathways ◽  
Normal Human Epidermal Keratinocytes ◽  
Normal Human ◽  
Related Proteins ◽  
Cytokeratin 14

AbstractObjectiveTo investigate the effect of mitogen-activated protein kinase (MAPK) signaling pathway in epidermal terminal differentiation.MethodsThe MAPK pathways (p38, ERK1/2, JNK) were inhibited by SB203580, PD98059, and SP600125 in normal human epidermal keratinocytes (NHEKs), respectively. Western blotting assays were performed to detect expression of filaggrin and differentiation-related proteins. The mRNA expressions of differentiation-related proteins were detected by real-time quantitative PCR (qRT-PCR).ResultsInhibition of MAPK pathway by SB203580, PD98059, and SP600125 resulted in significant reduction of filaggrin expression in NHEKs. Inhibition of the p38 MAPK pathway decreased the expression of differentiation-related proteins (cytokeratin 5, cytokeratin 14, ST14, and SPRR3), Akt, and NF-κB. Inhibition of JNK also suppressed expression of cytokeratin 14, SPRR3, Akt, and NF-κB. However, inhibition of ERK1/2 merely decreased expression of SPRR3 and Akt.ConclusionMAPK pathways regulates epidermal terminal differentiation in NHEKs. The p38 signaling pathway plays an especially important role.

scholarly journals Role of 11β-hydroxysteroid dehydrogenase type 1 in the development of atopic dermatitis

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Noo Ri Lee ◽  
Beom Jun Kim ◽  
Chung Hyeok Lee ◽  
Young Bin Lee ◽  
Solam Lee ◽  
...  
Keyword(s):  
Atopic Dermatitis ◽  
De Novo ◽  
Hydroxysteroid Dehydrogenase ◽  
Whole Body ◽  
Epidermal Keratinocytes ◽  
Human Epidermal Keratinocytes ◽  
Peripheral Tissues

AbstractGlucocorticoids (GCs) are potent anti-inflammatory drugs, the secretion of which is mediated and controlled by the hypothalamic–pituitary–adrenal axis. However, they are also secreted de novo by peripheral tissues for local use. Several tissues express 11β-hydroxysteroid dehydrogenase 1 (11β-HSD1), including the skin. The inactive GC cortisone is converted by 11β-HSD1 to active GC cortisol, which is responsible for delayed wound healing during a systemic excess of GC. However, the role of 11β-HSD1 in inflammation is unclear. We assessed whether 11β-HSD1 affects the development of atopic dermatitis (AD) in vitro and in vivo. The expression of 11β-HSD1 in the epidermis of AD lesions was higher than that in the epidermis of healthy controls. Knockdown of 11β-HSD1 in human epidermal keratinocytes increased the production of thymic stromal lymphopoietin. In an oxazolone-induced mouse model of AD, localized inhibition of 11β-HSD1 aggravated the development of AD and increased serum cytokine levels associated with AD. Mice with whole-body knockout (KO) of 11β-HSD1 developed significantly worse AD upon induction by oxazolone. We propose that 11β-HSD1 is a major factor affecting AD pathophysiology via suppression of atopic inflammation due to the modulation of active GC in the skin.

scholarly journals Neurotrophin-4 Production by Human Epidermal Keratinocytes: Increased Expression in Atopic Dermatitis

2000 ◽  
Vol 114 (6) ◽  
pp. 1108-1112 ◽  
Author(s):  
Markus Grewe ◽  
Kathrin Vogelsang ◽  
Thomas Ruzicka ◽  
Helger Stege ◽  
Jean Krutmann
Keyword(s):  
Atopic Dermatitis ◽  
Epidermal Keratinocytes ◽  
Human Epidermal Keratinocytes

scholarly journals Aryl Hydrocarbon Receptor Activation Downregulates IL-33 Expression in Keratinocytes via Ovo-Like 1

2020 ◽  
Vol 9 (3) ◽  
pp. 891 ◽  
Author(s):  
Gaku Tsuji ◽  
Akiko Hashimoto-Hachiya ◽  
Vu Hai Yen ◽  
Sho Miake ◽  
Masaki Takemura ◽  
...  
Keyword(s):  
Atopic Dermatitis ◽  
Aryl Hydrocarbon Receptor ◽  
Crucial Role ◽  
Receptor Activation ◽  
Epidermal Keratinocytes ◽  
Human Epidermal Keratinocytes ◽  
Aryl Hydrocarbon ◽  
Normal Human Epidermal Keratinocytes ◽  
Normal Human ◽  
Susceptible Gene

Background: IL-33, one of the IL-1 superfamily cytokines, has been shown to be associated with pruritus and inflammation in atopic dermatitis (AD). Furthermore, IL-33 production derived from keratinocytes reportedly has a crucial role in the development of AD; however, the mechanism of IL-33 expression has not been fully understood. Methods: We analyzed IL-33 expression in normal human epidermal keratinocytes (NHEKs) treated with IL-4. Results: IL-4 induced the upregulation of IL-33 expression in NHEKs. Based on the findings 1) that ovo-like 1 (OVOL1), a susceptible gene of AD, upregulates filaggrin (FLG) and loricrin (LOR) expression in NHEKs and 2) that reduced expression of FLG and LOR leads to production of IL-1 superfamily cytokines, we examined the involvement of OVOL1 in IL-33 expression in NHEKs. Knockdown of OVOL1 induced upregulation of IL-33 expression. Moreover, because Glyteer, an activator of aryl hydrocarbon receptor (AHR), reportedly upregulates OVOL1 expression, we examined whether treatment with Glyteer inhibited IL-33 expression in NHEKs. Treatment with Glyteer inhibited IL-4-induced upregulation of IL-33 expression, which was canceled by knockdown of either AHR or OVOL1. Conclusions: Activation of the AHR-OVOL1 axis inhibits IL-4-induced IL-33 expression, which could be beneficial for the treatment of AD.

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