scholarly journals Osthole Inhibits Expression of Genes Associated with Toll-like Receptor 2 Signaling Pathway in an Organotypic 3D Skin Model of Human Epidermis with Atopic Dermatitis

Cells ◽  
2021 ◽  
Vol 11 (1) ◽  
pp. 88
Author(s):  
Natalia Karolina Kordulewska ◽  
Justyna Topa ◽  
Robert Stryiński ◽  
Beata Jarmołowska
Keyword(s):  
Atopic Dermatitis ◽  
Signaling Pathway ◽  
Genetic Profile ◽  
Toll Like Receptor ◽  
Skin Model ◽  
Barrier Dysfunction ◽  
Gene Expressions ◽  
Expression Of Genes ◽  
3D Skin

The Toll-like receptor (TLR) family signature has been linked to the etiopathology of atopic dermatitis (AD), a chronic inflammatory skin disease associated with skin barrier dysfunction and immune system imbalance. We aimed to investigate whether osthole (a plant-derived compound) can inhibit the genetic profile of key genes associated with TLR2 signaling (TIRAP, MyD88, IRAK1, TRAF6, IκBα, NFκB) after stimulation with LPS or histamine in a 3D in vitro model of AD. Overexpression of the aforementioned genes may directly increase the secretion of proinflammatory cytokines (CKs) and chemokines (ChKs), which may exacerbate the symptoms of AD. Relative gene expressions were quantified by qPCR and secretion of CKs and ChKs was evaluated by ELISA assay. LPS and histamine increased the relative expression of genes related to the TLR2 pathway, and osthole successfully reduced it. In summary, our results show that osthole inhibits the expression of genes associated with the TLR signaling pathway in a skin model of AD. Moreover, the secretion of CKs and ChKs after treatment of AD with osthole in a 3D skin model in vitro suggests the potential of osthole as a novel compound for the treatment of AD.

scholarly journals Effect of Resveratrol-Enriched Rice on Skin Inflammation and Pruritus in the NC/Nga Mouse Model of Atopic Dermatitis

2019 ◽  
Vol 20 (6) ◽  
pp. 1428 ◽  
Author(s):  
Min Kang ◽  
Kyohee Cho ◽  
Jae Lee ◽  
Lalita Subedi ◽  
Silvia Yumnam ◽  
...  
Keyword(s):  
Atopic Dermatitis ◽  
Immunoglobulin E ◽  
Alternative Therapy ◽  
Human Keratinocytes ◽  
Skin Inflammation ◽  
Skin Lesions ◽  
Enzyme Linked Immunosorbent Assay ◽  
Skin Model ◽  
3D Skin

Resveratrol-enriched rice (RR) was developed using genetic engineering to combine the properties of resveratrol and rice. To evaluate the effect of RR on pruritic skin inflammation in atopic dermatitis (AD)-like skin lesions, we used dinitrochlorobenzene (DNCB)-induced NC/Nga mice and an in vitro 3D skin model. Normal rice (NR), resveratrol, and RR were topically applied to mice dorsal skin, following which the dermatitis index and scratching frequency were calculated. Histological examination was performed by hematoxylin and eosin and immunohistochemistry staining of IL-31 level. The level of immunoglobulin E (IgE) and IL-31 in the serum was determined by enzyme-linked immunosorbent assay (ELISA). The cytotoxicity of RR and the expression levels of pro-inflammatory cytokines were also determined in cultured human keratinocytes and a 3D skin model. RR significantly reduced scratching frequency, decreased the dermatitis severity and trans-epidermal water loss (TEWL) and improved skin hydration in DNCB-induced NC/Nga mice. RR also significantly decreased serum IL-31 and IgE levels and suppressed the production of IL-6 in human keratinocytes and the 3D skin model. Our study indicates that the synergistic effect of rice and resveratrol manifested by the topical application of RR can serve as a potential alternative therapy for chronic skin inflammatory diseases such as AD.

scholarly journals 299 Induction of an atopic dermatitis-like phenotype in a full-thickness in vitro human skin model

2020 ◽  
Vol 140 (7) ◽  
pp. S36
Author(s):  
J. Molignano ◽  
J. Oldach ◽  
K. Marengo ◽  
S. Ayehunie ◽  
M. Klausner
Keyword(s):  
Atopic Dermatitis ◽  
Human Skin ◽  
Full Thickness ◽  
Skin Model

Transcriptional gene expression profile in hepatocarcinoma cells induced by acetylsalicylic acid (ASA) in hepatitis C virus (HCV)-subgenomic replicon system.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e22016-e22016
Author(s):  
Clara Patricia Rios Ibarra ◽  
Barbara Verduzco Garza ◽  
Rocio Ortiz Lopez ◽  
Yohann Grondin ◽  
Sonia Lozano Sepulveda ◽  
...  
Keyword(s):  
Gene Expression ◽  
Signaling Pathway ◽  
Expression Profile ◽  
Molecular Mechanisms ◽  
Antiviral Effect ◽  
Subgenomic Replicon ◽  
Expression Of Genes ◽  
Antioxidant Agents ◽  
Hepatocarcinoma Cells

e22016 Background: It has been demonstrated that ASA treatment could down-regulate in vitro HCV expression in hepatocarcinoma cells (~50%, p 0.05). However, the signaling pathway induced during ASA antiviral effect has not been elucidated. We analyzed the transcriptional expression profile of Huh-7-HCV-subgenomic replicon cells in presence or absence of ASA in order to identify the signaling pathway and the molecular mechanisms involved in the antiviral effect induced by ASA on HCV expression. Methods: Huh-7-HCV-replicon cells (hepatocarcinoma) were exposed to 4 mM ASA from 24 to 72 hours. Total RNA was isolated, quantified and validated by capillary electrophoresis. After that, we performed a retrotranscription in vitro. Synthesized transcripts were marked with biotin, purified, fragmentized and hybridized in HG-U133 Plus 2 Gene Expression. Hybridization signals were captured with Gen Chip 3000 7G Scanner and analyzed by Expression Console and Dchit Software. Results: After normalization, we obtained hierarchical maps with differentially-expressed genes. Among genetic targets over-expressed, the following stood out CCAAT-enhancer-binding proteins (C/EBP), interleukine-8 (IL-8), cytochrome P450 (CyP450) and methallothioneins (MT) genes were found. Among down-regulated genes we identified ribonucleotide reductase (RR) and superoxide dismutase (SOD) genes. Some of these genes have been previously associated with oxidative stress regulation. All results were validated by real time PCR. Conclusions: We observed that ASA modulates the expression of genes associated with antioxidant role as SOD and methallothioneins. Antioxidant agents can inhibit virus proliferation. HCV decreased antioxidant defense, which promotes the development of hepatic complications caused by HCV infection, including liver cancer. Therefore, ASA could be inducing an antioxidant environment regulating HCV replication. This study provides a tool for identifying novel host factors in hepatocarcinoma cells involved in the antiviral effect regulated by ASA against HCV and improves our understanding of the regulatory mechanism of HCV replication.

scholarly journals Luteolin Targets the Toll-Like Receptor Signaling Pathway in Prevention of Hepatic and Adipocyte Fibrosis and Insulin Resistance in Diet-Induced Obese Mice

Nutrients ◽  
2018 ◽  
Vol 10 (10) ◽  
pp. 1415 ◽  
Author(s):  
Eun-Young Kwon ◽  
Myung-Sook Choi
Keyword(s):  
Insulin Resistance ◽  
Signaling Pathway ◽  
Low Grade ◽  
Toll Like Receptor ◽  
High Fat ◽  
Gene Expressions ◽  
Tlr Signaling ◽  
Low Grade Inflammation ◽  
Tlr Signaling Pathway

This study was to investigate the protective role of luteolin on inflammation-mediated metabolic diseases, focusing on the role of luteolin in the modulation of the Toll-like receptor (TLR) signaling pathway. C57BL/6J mice were fed a normal, high-fat, or high-fat + 0.005% (w/w) luteolin diet for 16 weeks. Luteolin improved chronic low-grade inflammation by modulating the TLR signaling pathway, resulting in reduced pro-inflammatory cytokines and macrophage accumulation. A positive relationship was detected between gene expressions of Tlr5, Map2k7, Mapk12, Mapk13, and Mapk9 and lipogenesis in epididymal white adipose tissue (eWAT) of luteolin-treated mice, which was linked to attenuation of hepatic lipotoxicity by increasing free fatty acid (FFA) flux to the WAT. Luteolin prevented fibrosis by decreasing extracellular matrix accumulation and cathepsin gene expressions, while enhancing the hepatic antioxidant system. Emr1 and Ccl7, important markers inducing low-grade inflammation, were affected by advanced age and greater body weight, which were normalized by luteolin treatment. Luteolin improved insulin resistance by normalizing pancreatic islet dysfunction and differentially modulating the plasma glucagon-like peptide-1 and gastric inhibitory polypeptide levels. Our results suggest that luteolin ameliorates diet-induced obesity and its comorbidities. Overall, this study provides novel insights into the effect of luteolin on the links among adiposopathy, insulin resistance, hepatic steatosis, and fibrosis.

scholarly journals LB1583 Induction of an atopic dermatitis-like phenotype in a full-thickness in vitro human skin model

2018 ◽  
Vol 138 (9) ◽  
pp. B20
Author(s):  
J. Molignano ◽  
K. Marengo ◽  
J. Oldach ◽  
G. Stolper ◽  
M. Li ◽  
...  
Keyword(s):  
Atopic Dermatitis ◽  
Human Skin ◽  
Full Thickness ◽  
Skin Model

scholarly journals 726 Induction of an atopic dermatitis-like phenotype in a full-thickness in vitro human skin model

2019 ◽  
Vol 139 (5) ◽  
pp. S124
Author(s):  
P. Hayden ◽  
S. Ayehunie ◽  
J. Oldach ◽  
M. Klausner
Keyword(s):  
Atopic Dermatitis ◽  
Human Skin ◽  
Full Thickness ◽  
Skin Model
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