Piceatannol, a resveratrol analog, attenuates Dermatophagoides farinae-induced atopic dermatitis like symptoms in NC/Nga mice

Background: Piceatannol is a resveratrol metabolite commonly found in red wine, grapes, and passion fruit seeds. Several studies have investigated the immune-modulating effects of piceatannol on processes related to allergic reactions. However, the relationship between piceatannol and atopic dermatitis (AD) has not yet been reported. Therefore, this study sought to investigate the effects of piceatannol in animal and cell line models. Methods: AD-like symptoms and skin lesions were induced by repeated topical application of Dermatophagoides farinae extract (DFE) on the skin of NC/Nga mice. Piceatannol was topically applied five times per week for four weeks. The molecular mechanism of piceatannol was studied in the TNFα/IFNγ-induced HaCaT cell line. Results: Topical application of piceatannol attenuated DFE-induced AD-like symptoms, as shown by skin thickness, dermatitis score, scratching time, and skin water loss. Histopathological analysis showed that piceatannol suppressed DFE-induced eosinophil and mast cell infiltration into the skin. These observations occurred concomitantly with the downregulation of inflammatory markers, including serum TARC, MDC, and IgE. In addition, piceatannol alleviated Th2 cytokines such as IL-4 and IL-13 in the skin tissue. Piceatannol decreased phosphorylation of JAK-STAT protein in the TNFα/IFNγ-induced HaCaT cell line. A molecular docking study showed that piceatannol strongly interacts with JAK1, suggesting a possible piceatannol mode of action. Conclusions: Piceatannol, a metabolite of resveratrol, has potential therapeutic efficacy in treating AD by targeting JAK1.

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Study of Anti-atopic Dermatitis Effects of Juice of Raphanus sativus var in HaCaT Cell Line

KSBB Journal ◽

10.7841/ksbbj.2017.32.4.311 ◽

2017 ◽

Vol 32 (4) ◽

pp. 311-318 ◽

Cited By ~ 1

Author(s):

Seung-Je Lee ◽

Eun-Gyeong Lim ◽

Ga-Yeon Kim ◽

Mi-Ji Jeon ◽

Sang-Yong Kim ◽

...

Keyword(s):

Atopic Dermatitis ◽

Cell Line ◽

Raphanus Sativus ◽

Hacat Cell ◽

Hacat Cell Line

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Impressic Acid Ameliorates Atopic Dermatitis-Like Skin Lesions by Inhibiting ERK1/2-Mediated Phosphorylation of NF-κB and STAT1

International Journal of Molecular Sciences ◽

10.3390/ijms22052334 ◽

2021 ◽

Vol 22 (5) ◽

pp. 2334

Author(s):

Jae Ho Choi ◽

Gi Ho Lee ◽

Sun Woo Jin ◽

Ji Yeon Kim ◽

Yong Pil Hwang ◽

...

Keyword(s):

Atopic Dermatitis ◽

Skin Lesions ◽

Histopathological Analysis ◽

Mrna Levels ◽

Chemokine Production ◽

Dermal Thickness ◽

Skin Symptoms ◽

Tnf Α ◽

Ifn Γ ◽

In Cells

Impressic acid (IPA), a lupane-type triterpenoid from Acanthopanax koreanum, has many pharmacological activities, including the attenuation of vascular endothelium dysfunction, cartilage destruction, and inflammatory diseases, but its influence on atopic dermatitis (AD)-like skin lesions is unknown. Therefore, we investigated the suppressive effect of IPA on 2,4-dinitrochlorobenzene (DNCB)-induced AD-like skin symptoms in mice and the underlying mechanisms in cells. IPA attenuated the DNCB-induced increase in the serum concentrations of IgE and thymic stromal lymphopoietin (TSLP), and in the mRNA levels of thymus and activation regulated chemokine(TARC), macrophage derived chemokine (MDC), interleukin-4 (IL-4), interleukin-5 (IL-5), interleukin-13 (IL-13), tumor necrosis factor-alpha (TNF-α) and interferon-gamma (IFN-γ) in mice. Histopathological analysis showed that IPA reduced the epidermal/dermal thickness and inflammatory and mast cell infiltration of ear tissue. In addition, IPA attenuated the phosphorylation of NF-κB and IκBα, and the degradation of IκBα in ear lesions. Furthermore, IPA treatment suppressed TNF-α/IFN-γ-induced TARC expression by inhibiting the NF-κB activation in cells. Phosphorylation of extracellular signalregulated protein kinase (ERK1/2) and the signal transducer and activator of transcription 1 (STAT1), the upstream signaling proteins, was reduced by IPA treatment in HaCaT cells. In conclusion, IPA ameliorated AD-like skin symptoms by regulating cytokine and chemokine production and so has therapeutic potential for AD-like skin lesions.

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Gomisin M2 Ameliorates Atopic Dermatitis-like Skin Lesions via Inhibition of STAT1 and NF-κB Activation in 2,4-Dinitrochlorobenzene/Dermatophagoides farinae Extract-Induced BALB/c Mice

Molecules ◽

10.3390/molecules26154409 ◽

2021 ◽

Vol 26 (15) ◽

pp. 4409

Author(s):

Jinjoo Kang ◽

Soyoung Lee ◽

Namkyung Kim ◽

Hima Dhakal ◽

Taeg-Kyu Kwon ◽

...

Keyword(s):

Atopic Dermatitis ◽

Oral Administration ◽

Skin Diseases ◽

Nuclear Translocation ◽

Skin Lesions ◽

Biologically Active ◽

Therapeutic Effects ◽

Dermatophagoides Farinae ◽

Tnf Α ◽

Ifn Γ

The extracts of Schisandra chinensis (Turcz.) Baill. (Schisandraceae) have various therapeutic effects, including inflammation and allergy. In this study, gomisin M2 (GM2) was isolated from S. chinensis and its beneficial effects were assessed against atopic dermatitis (AD). We evaluated the therapeutic effects of GM2 on 2,4-dinitrochlorobenzene (DNCB) and Dermatophagoides farinae extract (DFE)-induced AD-like skin lesions with BALB/c mice ears and within the tumor necrosis factor (TNF)-α and interferon (IFN)-γ-stimulated keratinocytes. The oral administration of GM2 resulted in reduced epidermal and dermal thickness, infiltration of tissue eosinophils, mast cells, and helper T cells in AD-like lesions. GM2 suppressed the expression of IL-1β, IL-4, IL-5, IL-6, IL-12a, and TSLP in ear tissue and the expression of IFN-γ, IL-4, and IL-17A in auricular lymph nodes. GM2 also inhibited STAT1 and NF-κB phosphorylation in DNCB/DFE-induced AD-like lesions. The oral administration of GM2 reduced levels of IgE (DFE-specific and total) and IgG2a in the mice sera, as well as protein levels of IL-4, IL-6, and TSLP in ear tissues. In TNF-α/IFN-γ-stimulated keratinocytes, GM2 significantly inhibited IL-1β, IL-6, CXCL8, and CCL22 through the suppression of STAT1 phosphorylation and the nuclear translocation of NF-κB. Taken together, these results indicate that GM2 is a biologically active compound that exhibits inhibitory effects on skin inflammation and suggests that GM2 might serve as a remedy in inflammatory skin diseases, specifically on AD.

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Topical Application of Eupatilin Ameliorates Atopic Dermatitis-Like Skin Lesions in NC/Nga Mice

Annals of Dermatology ◽

10.5021/ad.2017.29.1.61 ◽

2017 ◽

Vol 29 (1) ◽

pp. 61 ◽

Cited By ~ 7

Author(s):

Ji Hyun Lee ◽

Ye Jin Lee ◽

Jun Young Lee ◽

Young Min Park

Keyword(s):

Atopic Dermatitis ◽

Topical Application ◽

Skin Lesions

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Normal keratinization in a spontaneously immortalized aneuploid human keratinocyte cell line.

The Journal of Cell Biology ◽

10.1083/jcb.106.3.761 ◽

1988 ◽

Vol 106 (3) ◽

pp. 761-771 ◽

Cited By ~ 2754

Author(s):

P Boukamp ◽

R T Petrussevska ◽

D Breitkreutz ◽

J Hornung ◽

A Markham ◽

...

Keyword(s):

Epithelial Cell ◽

Cell Line ◽

Human Skin ◽

Cell Lines ◽

Hacat Cell ◽

Epithelial Cell Line ◽

Spontaneous Transformation ◽

Chromosomal Alterations ◽

Hacat Cell Line

In contrast to mouse epidermal cells, human skin keratinocytes are rather resistant to transformation in vitro. Immortalization has been achieved by SV40 but has resulted in cell lines with altered differentiation. We have established a spontaneously transformed human epithelial cell line from adult skin, which maintains full epidermal differentiation capacity. This HaCaT cell line is obviously immortal (greater than 140 passages), has a transformed phenotype in vitro (clonogenic on plastic and in agar) but remains nontumorigenic. Despite the altered and unlimited growth potential, HaCaT cells, similar to normal keratinocytes, reform an orderly structured and differentiated epidermal tissue when transplanted onto nude mice. Differentiation-specific keratins (Nos. 1 and 10) and other markers (involucrin and filaggrin) are expressed and regularly located. Thus, HaCaT is the first permanent epithelial cell line from adult human skin that exhibits normal differentiation and provides a promising tool for studying regulation of keratinization in human cells. On karyotyping this line is aneuploid (initially hypodiploid) with unique stable marker chromosomes indicating monoclonal origin. The identity of the HaCaT line with the tissue of origin was proven by DNA fingerprinting using hypervariable minisatellite probes. This is the first demonstration that the DNA fingerprint pattern is unaffected by long-term cultivation, transformation, and multiple chromosomal alterations, thereby offering a unique possibility for unequivocal identification of human cell lines. The characteristics of the HaCaT cell line clearly document that spontaneous transformation of human adult keratinocytes can occur in vitro and is associated with sequential chromosomal alterations, though not obligatorily linked to major defects in differentiation.

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Inter-Relationship between Low-Dose Hyper-Radiosensitivity and Radiation-Induced Bystander Effects in the Human T98G Glioma and the Epithelial HaCaT Cell Line

Radiation Research ◽

10.1667/rr14208.1 ◽

2016 ◽

Vol 185 (2) ◽

pp. 124-133 ◽

Cited By ~ 27

Author(s):

Cristian Fernandez-Palomo ◽

Colin Seymour ◽

Carmel Mothersill

Keyword(s):

Cell Line ◽

Low Dose ◽

Hacat Cell ◽

Bystander Effects ◽

Hacat Cell Line ◽

Radiation Induced

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Topical Application of Doxycycline Inhibits Th2 Cell Development Mediated by Langerhans Cells and Exerts a Therapeutic Effect on Atopic Dermatitis

Journal of Pharmacy & Pharmaceutical Sciences ◽

10.18433/jpps30847 ◽

2020 ◽

Vol 23 ◽

pp. 86-99 ◽

Cited By ~ 1

Author(s):

Katsuhiko Matsui ◽

Yuki Nojima ◽

Yuka Kajiwara ◽

Kana Busujima ◽

Yuki Mori

Keyword(s):

Atopic Dermatitis ◽

Lymph Nodes ◽

Topical Application ◽

Severity Score ◽

Langerhans Cells ◽

Skin Lesions ◽

Cell Development ◽

Th2 Cells ◽

Th2 Cytokines ◽

Th2 Cell

Background: Langerhans cells (LCs) polarize the immune milieu towards a T helper type (Th) 1 or Th2 immune response. We investigated the effects of selected tetracyclines on Th cells development mediated by LCs, and their implications for the treatment of atopic dermatitis (AD). Methods: Mice were primed with ovalbumin (OVA) peptide-pulsed LCs, which had been treated with each antibiotic, via the hind footpad. After 5 days, the Th1/Th2 cytokine response in the popliteal lymph nodes was investigated by enzyme-linked immunosorbent assay. The expression of cell surface molecules on LCs was investigated using reverse transcriptase polymerase chain reaction. The therapeutic effects of a selected antibiotic on AD-like skin lesions of NC/Nga mice were assessed in terms of the skin severity score, histological changes in the lesioned skin, the serum level of total IgE, and expression of Th1/Th2 cytokines in lymph nodes and skin lesions. Results: Antibiotic-treated, OVA peptide-pulsed LCs inhibited development of Th2 cells but not Th1 cells. This was accompanied by suppression of T-cell immunoglobulin and mucin domain-containing protein (TIM)-4 expression in LCs. Doxycycline had the greatest activity against Staphylococcus aureus strains isolated from skin lesions of patients with AD, and a strong inhibitory effect on Th2 cell development. Doxycycline suppressed the increase in the skin severity score during the acute phase in NC/Nga mice similar to betamethasone. This suppressive effect was associated with a decrease in the serum IgE level and production of Th2 cytokines in auricular lymph node cells and skin lesions. Conclusion: Topical application of doxycycline to AD lesions would act on both superficial S. aureus colonization and epidermal LCs, thus possibly inhibiting the development of Th2 cells in vivo, with benefits for control of acute inflammation in AD.

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