The Effect of Cyclosporine A on Dermal Fibroblast Cell - Transcriptomic Analysis of Inflammatory Response Pathway

2020 ◽  
Vol 21 (12) ◽  
pp. 1213-1223
Author(s):  
Grażyna Janikowska ◽  
Ewa Kurzeja ◽  
Marcin Janikowski ◽  
Barbara Strzałka-Mrozik ◽  
Alina Pyka-Pająk ◽  
...  
Keyword(s):  
Inflammatory Response ◽  
Cyclosporine A ◽  
Dermal Fibroblast ◽  
Dermal Fibroblasts ◽  
Transcriptional Level ◽  
Main Task ◽  
Human Dermal Fibroblasts ◽  
Therapeutic Concentration ◽  
Cutaneous Manifestations ◽  
Sites Of Action

Background: The first immunosuppressive drug - cyclosporine A (CsA) has many unquestioned merits in maintaining organ transplants in patients, as well as, in the treatment of many inflammatory diseases, also associated with cutaneous manifestations. The main task of this drug is to suppress the inflammatory response at the sites of action, which is not well known. Objective: The objective of this study was to evaluate the influence of CsA in therapeutic concentration on the expression of genes associated with the inflammatory response pathway in normal human dermal fibroblasts (NHDF; CC-2511), and this study attempted to determine the mechanism of its action. Methods: The cytotoxicity MTT test was performed. The expression of the inflammatory response pathway genes was determined using HG-U133A_2.0 oligonucleotide microarrays. Statistical analysis was performed by GeneSpring 13.0 software using the PL-Grid platform. Results: Among the 5,300 mRNA, only 573 were changed significantly in response to CsA compared to the control fibroblasts (P≤0.05). CsA inhibited the expression of most genes associated with the inflammatory response in NHDFs. There were only 19 genes with a fold change (FC) lower than -2.0, among which EGR1, FOS, PBK, CDK1 and TOP2A had the lowest expression, as did CXCL2 which can directly impact inflammation. Furthermore, ZNF451 was strongly induced, and COL1A1, COL3A1, IL33, TNFRSFs were weakly up-regulated (FC lower than 2.0). Conclusion: The CsA in therapeutic concentration influences the genes linked to the inflammatory response (in the transcriptional level) in human dermal fibroblasts. The findings suggest that the potential mechanism of CsA action in this concentration and on these genes can be associated with a profibrotic and proapoptotic, and genotoxic effects.

scholarly journals A Phytocomplex Consisting of Tropaeolum majus L. and Salvia officinalis L. Extracts Alleviates the Inflammatory Response of Dermal Fibroblasts to Bacterial Lipopolysaccharides

2020 ◽  
Vol 2020 ◽  
pp. 1-14 ◽  
Author(s):  
Tunde Jurca ◽  
Ioana Baldea ◽  
Gabriela Adriana Filip ◽  
Diana Olteanu ◽  
Simona Clichici ◽  
...  
Keyword(s):  
Transcription Factors ◽  
Inflammatory Response ◽  
Dermal Fibroblast ◽  
Physicochemical Characterization ◽  
Antibacterial Activities ◽  
Dermal Fibroblasts ◽  
High Dose ◽  
Cytokine Levels ◽  
Bacterial Lipopolysaccharides

Background. The antimicrobial activity and effects of a phytocomplex consisting of Tropaeolum flos (T) and Salviae folium (S) extracts on the cytokine levels and transcription factors on dermal fibroblast BJ exposed to bacterial lipopolysaccharides were examined. Methods. In order to select the most optimal combination ratio of the two extracts for using in vitro, the physicochemical characterization of vegetal extract mixtures was performed and the antioxidant and antibacterial activities were evaluated on five different formulations of T : S, namely, 1 : 1, 1 : 2, 2 : 1, 3 : 1, and 1 : 3. The best combination of bioactive compounds with regard to antioxidant and antibacterial activities (T : S 1 : 2) was selected for in vitro evaluation of the anti-inflammatory effect. Human dermal fibroblast BJ cells were treated with two doses of the extract mixture and then exposed to bacterial lipopolysaccharides (LPS). The levels of the cytokines involved in inflammatory response, namely, interleukin- (IL-) 6, tumor necrosis factor- (TNF-) α, IL-31, and IL-33, were quantified by ELISA, and the expression of transcription factors, namely, signal transducer and activator of transcription (STAT) 3, nuclear factor kappa B (NFκB), and phosphorylated NFκB (pNFκB), were evaluated by western blot analysis. Results. The results have shown that the mixture of T : S 1 : 2 exhibited significant antibacterial effects on Staphylococcus aureus ATCC 25923. LPS exposure increased the cytokine levels in BJ cells and enhanced the NFκB expression. The pretreatment of BF cells exposed to LPS with the two doses of the extract mixture markedly inhibited the increase of IL-33 and TNF-α levels and amplified the NFκB expression and its activation, especially with the high dose. The low doses of the extract reduced NFκB expression but increased its activation. Conclusions. These experimental findings suggest that the mixture of T : S 1 : 2 can exert some protection against bacterial infections and inflammation induced by LPS in BJ cells being a good therapeutic option in related conditions associated with inflammation.

scholarly journals Puerarin blocks the aging phenotype in human dermal fibroblasts

PLoS ONE ◽  
2021 ◽  
Vol 16 (4) ◽  
pp. e0249367
Author(s):  
Yuki Kamiya ◽  
Mao Odama ◽  
Aki Mizuguti ◽  
Shigeru Murakami ◽  
Takashi Ito
Keyword(s):  
Dermal Fibroblast ◽  
Smooth Muscle Actin ◽  
Dermal Fibroblasts ◽  
Human Dermal Fibroblasts ◽  
High Passage ◽  
Normal Human ◽  
Low Passage ◽  
Passage Cells ◽  
Beta Galactosidase ◽  
Functional Defects

Dermal fibroblast aging contributes to aging-associated functional defects in the skin since dermal fibroblasts maintain skin homeostasis by interacting with the epidermis and extracellular matrix. Here, we found that puerarin, an isoflavone present in Pueraria lobata (Kudzu), can prevent the development of the aging-phenotype in human dermal fibroblasts. Normal human dermal fibroblasts (NHDFs) were subcultivated and high-passage cells were selected as senescent cells, whereas low-passage cells were selected as a young cell control. Puerarin treatment increased cell proliferation and decreased the proportion of senescence-associated beta-galactosidase-positive cells in a high-passage culture of NHDFs. Moreover, puerarin treatment reduced the number of smooth muscle actin (SMA)-positive myofibroblasts and the expression of a reticular fibroblast marker, calponin 1 (CNN1), which were induced in high-passage NHDFs. Fulvestrant, an estrogen receptor antagonist, blocked the puerarin-mediated downregulation of SMA and CNN1. Our results suggest that puerarin may be a useful functional food that alleviates aging-related functional defects in dermal fibroblasts.

scholarly journals Puerarin blocks aging phenotype in cultured human dermal fibroblasts

2020 ◽  
Author(s):  
Yuki Kamiya ◽  
Mao Odama ◽  
Aki Mizuguti ◽  
Shigeru Murakami ◽  
Takashi Ito
Keyword(s):  
Dermal Fibroblast ◽  
Smooth Muscle Actin ◽  
Dermal Fibroblasts ◽  
Pueraria Lobata ◽  
Human Dermal Fibroblasts ◽  
Proliferating Cells ◽  
Food Factor ◽  
High Passage ◽  
Beta Galactosidase ◽  
Functional Defects

AbstractDermal fibroblast aging contributes to aging-associated functional defects in the skin since dermal fibroblasts are important to maintain skin homeostasis by interacting with epidermis and extracellular matrix. Here we identified that puerarin, an isoflavone contained in Pueraria lobata (Kudzu), can prevent the aging-phenotype of human dermal fibroblasts. Puerarin treatment increased in proliferating cells and decreased in senescence-associated beta-galactosidase positive cells in the high-passage culture of dermal fibroblasts. Moreover, puerarin reduced smooth muscle actin-positive myofibroblasts and the expression of a reticular fibroblast marker, calponin 1 (CNN1), which were induced in high-passage fibroblasts. Fulvestrant, an estrogen receptor antagonist, blocked puerarin-mediated downregulation of SMA and CNN1. Our results suggest that puerarin may be a useful food factor that alleviates aging-related functional defects in the skin.

scholarly journals Primary Ciliogenesis by 2-Isopropylmalic Acid Prevents PM2.5-Induced Inflammatory Response and MMP-1 Activation in Human Dermal Fibroblasts and a 3-D-Skin Model

2021 ◽  
Vol 22 (20) ◽  
pp. 10941
Author(s):  
Ji-Eun Bae ◽  
Daejin Min ◽  
Ji Yeon Choi ◽  
Hyunjung Choi ◽  
Joon Bum Kim ◽  
...  
Keyword(s):  
Inflammatory Response ◽  
Primary Cilia ◽  
Dermal Fibroblasts ◽  
Oxygen Species ◽  
Human Dermal Fibroblasts ◽  
Skin Model ◽  
Skin Cells ◽  
Tnf Α ◽  
Stress Kinase ◽  
Pro Inflammatory Cytokines

Particulate matters (PMs) increase oxidative stress and inflammatory response in different tissues. PMs disrupt the formation of primary cilia in various skin cells, including keratinocytes and melanocytes. In this study, we found that 2-isopropylmalic acid (2-IPMA) promoted primary ciliogenesis and restored the PM2.5-induced dysgenesis of primary cilia in dermal fibroblasts. Moreover, 2-IPMA inhibited the generation of excessive reactive oxygen species and the activation of stress kinase in PM2.5-treated dermal fibroblasts. Further, 2-IPMA inhibited the production of pro-inflammatory cytokines, including IL-6 and TNF-α, which were upregulated by PM2.5. However, the inhibition of primary ciliogenesis by IFT88 depletion reversed the downregulated cytokines by 2-IPMA. Moreover, we found that PM2.5 treatment increased the MMP-1 expression in dermal fibroblasts and a human 3-D-skin model. The reduced MMP-1 expression by 2-IPMA was further reversed by IFT88 depletion in PM2.5-treated dermal fibroblasts. These findings suggest that 2-IPMA ameliorates PM2.5-induced inflammation by promoting primary ciliogenesis in dermal fibroblasts.

scholarly journals Bactericidal/Permeability-Increasing Protein Is Expressed by Human Dermal Fibroblasts and Upregulated by Interleukin 4

2003 ◽  
Vol 10 (3) ◽  
pp. 473-475 ◽  
Author(s):  
Philipp H. Reichel ◽  
Christine Seemann ◽  
Elena Csernok ◽  
Jens-M. Schröder ◽  
Antje Müller ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Dermal Fibroblast ◽  
Constitutive Expression ◽  
Human Dermal Fibroblast ◽  
Dermal Fibroblasts ◽  
Interleukin 4 ◽  
Human Dermal Fibroblasts ◽  
Bacterial Clearance ◽  
Gram Negative

ABSTRACT The bactericidal/permeability-increasing protein (BPI) is an antibiotic- and endotoxin-neutralizing protein of granulocytes and epithelial cells. Constitutive expression of BPI, which increases upon interleukin 4 stimulation, by human dermal fibroblast was demonstrated, suggesting an important role of BPI in gram-negative bacterial clearance and a dampened response to endotoxin in the skin.

CYTOTOXIC ASSESSMENT OF L-ASCORBIC ACID/MONTMORILLONITE UPON HUMAN DERMAL FIBROBLASTS IN VITRO: MTT ACTIVITY ASSAY

2008 ◽  
Vol 20 (06) ◽  
pp. 337-343
Author(s):  
Yuan-Haun Lee ◽  
Bor-Yann Chen ◽  
Feng-Huei Lin ◽  
Kun-Yu Lin ◽  
King-Fu Lin
Keyword(s):  
Ascorbic Acid ◽  
Phosphoric Acid ◽  
Dermal Fibroblast ◽  
Fibroblast Cell ◽  
Human Dermal Fibroblast ◽  
Dermal Fibroblasts ◽  
Human Dermal Fibroblasts ◽  
Cytotoxic Effects ◽  
Black Spots

This first-attempt study tended to inspect the cytotoxic effects of montmorillonite (MMT) or 0.01 N phosphoric acid treated MMT supplemented with L-ascorbic acid (LAA) upon human dermal fibroblasts for possible applications. Light micrographs of human dermal fibroblast cell cultures revealed that more dense black spots in larger sizes were observed when higher levels of MMT were supplemented into the fibroblast culture, indicating that more dermal fibroblasts were covered by MMT particles. Compared with the supplementation of LAA alone, this study selected mitochondrial dehydrogenase activity (MTT) assay as an indicator bioreaction to show possible cytotoxic (or allergic) responses upon human dermal fibroblasts in vitro when LAA/acid-treated MMT composites were added. Statistical analysis showed that LAA augmented with either MMT or 0.01 N phosphoric-acid-treated MMT provoked insignificant cytotoxic responses to human dermal fibroblasts. Thus, an augmentation of MMT or 0.01 N phosphoric-acid-treated MMT to LAA should be biologically feasible for possible skin applications according to this human dermal fibroblasts model.

scholarly journals Pengaruh Glukosa Tinggi terhadap Proliferasi, Migrasi dan Ekspresi Gen OCT-4 pada Kultur Sel Dermal Fibroblast Manusia

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Restu Syamsul Hadi ◽  
Yurika Sandra
Keyword(s):  
Dermal Fibroblast ◽  
Dermal Fibroblasts ◽  
Human Dermal Fibroblasts ◽  
Minimal Essential Medium ◽  
Rt Pcr ◽  
Scratch Assay

Human dermal fibroblasts (HDF) termasuk sel mesenchymal yang diisolasi dari lapisan dermis kulit. HDF berpotensi digunakan untuk pengobatan penyembuhan luka berdasarkan pengobatan regeneratif. Peningkatan konsentrasi glukosa dapat merusak fungsi sel dan menghambat terapi penyembuhan luka. Penelitian ini dilakukan untuk mengkaji pengaruh glukosa tinggi pada proliferasi, migrasi dan ekspresi gen OCT-4 sel HDF sebagai model penyembuhan luka diabetes in vitro. Pada penelitian eksperimental ini, fibroblast diisolasi dari kulit setelah sirkumsisi, kemudian ditumbuhkan dalam medium Minimal Essential Medium (DMEM) Dulbecco lengkap dengan serum 10%. Untuk menguji efek glukosa tinggi pada proliferasi sel HDF dilakukan dengan uji CCK-8. Migrasi sel HDF dievaluasi menggunakan uji scratch-assay. RT-PCR digunakan untuk menentukan ekspresi gen OCT-4.  Hasilnya menunjukkan bahwa glukosa tinggi (25 mM-50 mM) meningkatkan kemampuan proliferasi dan migrasi sel HDF. Efek glukosa tinggi tergantung pada dosis. Perlakuan glukosa pada dosis 75 mM akan menghambat kemampuan pertumbuhan HDF. Ekspresi gen OCT-4 meningkat secara bermakna pada pemberian glukosa dosis 25-50 mM. Hasil penelitian ini memberikan dasar untuk pengembangan terapi dalam kondisi diabetes bahwa terapi sel HDF dapat meningkatkan penyembuhan luka meskipun dalam kondisi glukosa tinggi.

Effect of (1→3)(1→6)-Β-Glucan Containing PLGA Scaffold on Human Dermal Fibroblast Attachment and Proliferation

2007 ◽  
Vol 342-343 ◽  
pp. 377-380 ◽  
Author(s):  
Sang Gil Lee ◽  
Jung Bok Lee ◽  
Jong Chul Park ◽  
Young Il Yang ◽  
Jeong Koo Kim
Keyword(s):  
Cell Proliferation ◽  
Dermal Fibroblast ◽  
Human Dermal Fibroblast ◽  
Dermal Fibroblasts ◽  
Human Dermal Fibroblasts ◽  
Plga Scaffold ◽  
Salt Leaching ◽  
Before And After ◽  
Fibroblast Attachment ◽  
Scanning Electron

The effect of β-glucan-reinforced PLGA scaffold on cell proliferation was investigated. The PLGA scaffolds were prepared by salt-leaching method. The prepared scaffolds were grafted with (1→3) (1→6)-β-glucan in various ratios after plasma treatment on the surface. The surface of the scaffold was characterized by scanning electron microscope (SEM). The HDFs (Human dermal fibroblasts, 1105 cells/scaffold) were used to evaluate the cell proliferation on PLGA scaffold before and after plasma/β-glucan treatment. In results, in the β-glucan treated scaffolds, the pores seemed to become narrower and even looked like closed form. The result of cell proliferation showed that the plasma/β-glucan treated scaffolds had narrower pores because the β-glucan was attached in the pores that would not be allowed the cells to penetrate into the inner areas. Consequently, cell proliferation was not effective in the plasma/β-glucan treated scaffolds in this study.

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