Artykuły w czasopismach: „Human dermal fibroblasts”

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Lee, Yuan-Haun, Bor-Yann Chen, Feng-Huei Lin, Kun-Yu Lin i King-Fu Lin. "CYTOTOXIC ASSESSMENT OF L-ASCORBIC ACID/MONTMORILLONITE UPON HUMAN DERMAL FIBROBLASTS IN VITRO: MTT ACTIVITY ASSAY". Biomedical Engineering: Applications, Basis and Communications 20, nr 06 (grudzień 2008): 337–43. http://dx.doi.org/10.4015/s1016237208000957.

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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.

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Kamiya, Yuki, Mao Odama, Aki Mizuguti, Shigeru Murakami i Takashi Ito. "Puerarin blocks the aging phenotype in human dermal fibroblasts". PLOS ONE 16, nr 4 (22.04.2021): e0249367. http://dx.doi.org/10.1371/journal.pone.0249367.

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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.

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Azab, Ehab, i Abdel-Rahman Youssef. "Biocompatibility Evaluation of Human and Porcine Acellular Dermal Matrix on Human Primary Gingival Fibroblasts: In Vitro Comparative Study". European Journal of Dentistry 15, nr 03 (18.06.2021): 563–67. http://dx.doi.org/10.1055/s-0041-1727551.

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Abstract Objective Allogeneic and xenogeneic acellular dermal matrix (ADM) grafts have been used to treat periodontal soft tissue defects. The purpose of the current study was to compare the effect of human ADM (AlloDerm) and porcine ADM (Derma) on human primary gingival fibroblasts in vitro regarding the biocompatibility test. Materials and Methods Gingival fibroblasts were obtained from healthy adult gingiva and seeded on AlloDerm or Derma ADM in 96-well plate. The control cells were grown on a surface-treated polystyrene cell-culture plate without matrix. The cells were cultured for 3, 7, and 14 days. The fibroblasts morphology was examined using inverted microscopy, and the cell viability of fibroblasts adherent to the dermal matrix was evaluated using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) cell viability assay after 3, 7, and 14 days in culture. The data were statistically evaluated by one-way analysis of variance. p-Value of 0.05 was considered significant. Results Gingival fibroblasts adjacent to the AlloDerm and Derma matrices were healthy, attached to the well, and did not exhibit any cytopathic changes similar to control. There were no statistically significant differences in the cell viability between the gingival fibroblasts attached to Derma and AlloDerm on day 3 (p = 0.841), day 7 (p = 0.198), and day 14 (p = 0.788). Conclusion Considering this in vitro study’s limitations, both human and porcine ADM were compatible with the surrounding human primary gingival fibroblasts. No significant differences were observed in the cell viability between the gingival fibroblasts that were attached to Derma and AlloDerm.

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Akers, Ian A., Maddy Parsons, Michael R. Hill, Morley D. Hollenberg, Shahin Sanjar, Geoffrey J. Laurent i Robin J. McAnulty. "Mast cell tryptase stimulates human lung fibroblast proliferation via protease-activated receptor-2". American Journal of Physiology-Lung Cellular and Molecular Physiology 278, nr 1 (1.01.2000): L193—L201. http://dx.doi.org/10.1152/ajplung.2000.278.1.l193.

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Mast cells play a potentially important role in fibroproliferative diseases, releasing mediators including tryptase that are capable of stimulating fibroblast proliferation and procollagen synthesis. The mechanism by which tryptase stimulates fibroblast proliferation is unclear, although recent studies suggest it can activate protease-activated receptor (PAR)-2. We therefore investigated the role of PAR-2 in tryptase-induced proliferation of human fetal lung and adult lung parenchymal and airway fibroblasts and, for comparative purposes, adult dermal fibroblasts. Tryptase (0.7–70 mU/ml) induced concentration-dependent increases in proliferation of all fibroblasts studied. Antipain, bis(5-amidino-2-benzimidazolyl)methane, and benzamidine inhibited tryptase-induced fibroblast proliferation, demonstrating that proteolytic activity is required for the proliferative effects of tryptase. RT-PCR demonstrated the presence of PAR-2 mRNA, and immunohistochemical staining localized PAR-2 to the cell surface of lung fibroblasts. In addition , specific PAR-2 activating peptides, SLIGKV and SLIGRL, mimicked the proliferative effects of tryptase. In contrast, human dermal fibroblasts only weakly stained with the PAR-2 antibody, PAR-2 mRNA was almost undetectable, and fibroblasts did not respond to PAR-2 activating peptides. These results suggest that tryptase induces lung, but not dermal, fibroblast proliferation via activation of PAR-2 and are consistent with the hypothesis that the release of tryptase from activated mast cells may play an important role in the fibroproliferative response observed in asthma, chronic obstructive pulmonary disease, and patients with pulmonary fibrosis.

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Kim, Jihee, Bomi Kim, Soo Kim, Chae Yang, Seung Song, Won Lee i Ju Lee. "Hypoxia-Induced Epithelial-To-Mesenchymal Transition Mediates Fibroblast Abnormalities via ERK Activation in Cutaneous Wound Healing". International Journal of Molecular Sciences 20, nr 10 (24.05.2019): 2546. http://dx.doi.org/10.3390/ijms20102546.

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Previous studies described the involvement of extracellular signal-related kinase (ERK) in systemic fibrotic diseases, but the role of ERK in cutaneous scarring is unknown. Although hypoxia drives tissue fibrosis by activating hypoxia-inducible factor-1α (HIF-1α), the specific roles of hypoxia and associated ERK phosphorylation in abnormal fibroblast activity during cutaneous scarring are unclear. Here, we investigated whether pathologic myofibroblast-like keloid fibroblast activity is promoted by hypoxia-induced epithelial–mesenchymal transition mediated by ERK activation. ERK phosphorylation was significantly increased in keloid tissue and fibroblasts. Human dermal fibroblasts cultured under hypoxia (1% O2) expressed phosphorylated ERK and exhibited activation of p38 mitogen-activated protein kinase signaling. Hypoxic human dermal fibroblasts showed increased protein and mRNA levels of epithelial–mesenchymal transition markers. Furthermore, administration of an ERK inhibitor (SCH772984) reduced the hypoxia-induced elevation of collagen type I levels in human dermal fibroblasts. Therefore, ERK may be a promising therapeutic target in profibrogenic diseases.

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Tverdokhlib, I. V., i Yu V. Silkina. "Dermal fibroblasts: the terminology, heterogeneity of subpopulations and common properties". Morphologia 14, nr 4 (25.09.2021): 108–14. http://dx.doi.org/10.26641/1997-9665.2020.4.108-114.

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Dermal fibroblasts are a dynamic and diverse population of cells whose functions in skin in many respects remain unknown. Normal adult human skin contains at least three distinct subpopulations of fibroblasts, which occupy unique niches in the dermis. Fibroblasts from each of these niches exhibit distinctive differences when cultured separately. Specific differences in fibroblast histophysiology are evident in papillary dermal fibroblasts, which reside in the superficial dermis, and reticular fibroblasts, which reside in the deep dermis. Both of these subpopulations of fibroblasts differ from the fibroblasts that are associated with hair follicles. Fibroblasts engage in fibroblast-epidermal interactions during hair development and in interfollicular regions of skin. They also play an important role in cutaneous structural transformations.

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Woodley, David T., John R. Stanley, Melinda J. Reese i Edward J. O'keefe. "Human Dermal Fibroblasts Synthesize Laminin". Journal of Investigative Dermatology 90, nr 5 (maj 1988): 679–83. http://dx.doi.org/10.1111/1523-1747.ep12560880.

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Nickel, Kimberly, Ursula Wensorra, Horst Wenck, Nils Peters i Harald Genth. "Evaluation of Immunomodulatory Responses and Changed Wound Healing in Type 2 Diabetes—A Study Exploiting Dermal Fibroblasts from Diabetic and Non-Diabetic Human Donors". Cells 10, nr 11 (28.10.2021): 2931. http://dx.doi.org/10.3390/cells10112931.

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The dermis is the connective layer between the epidermis and subcutis and harbours nerve endings, glands, blood vessels, and hair follicles. The most abundant cell type is the fibroblast. Dermal fibroblasts have a versatile portfolio of functions within the dermis that correspond with different types of cells by either direct contact or by autocrine and paracrine signalling. Diabetic skin is characterized by itching, numbness, ulcers, eczema, and other pathophysiological changes. These pathogenic phenotypes have been associated with the effects of the reactive glucose metabolite methylglyoxal (MGO) on dermal cells. In this study, dermal fibroblasts were isolated from diabetic and non-diabetic human donors. Cultured dermal fibroblasts from diabetic donors exhibited reduced insulin-induced glucose uptake and reduced expression of the insulin receptor. This diabetic phenotype persists under cell culture conditions. Secretion of IL-6 was increased in fibroblasts from diabetic donors. Increased secretion of IL-6 and MIF was also observed upon the treatment of dermal fibroblasts with MGO, suggesting that MGO is sufficient for triggering these immunomodulatory responses. Remarkably, MIF treatment resulted in decreased activity of MGO-detoxifying glyoxalase-1. Given that reduced glyoxalase activity results in increased MGO levels, these findings suggested a positive-feedback loop for MGO generation, in which MIF, evoked by MGO, in turn blocks MGO-degrading glyoxalase activity. Finally, secretion of procollagen Type I C-Peptide (PICP), a marker of collagen production, was reduced in fibroblast from diabetic donors. Remarkably, treatment of fibroblasts with either MGO or MIF was sufficient for inducing reduced PICP levels. The observations of this study unravel a signalling network in human dermal fibroblasts with the metabolite MGO being sufficient for inflammation and delayed wound healing, hallmarks of T2D.

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Li, Jinglei, Tao Tong, Du-Ock Ko, Dong-Ok Chung, Won-Chul Jeong, Ji-Eun Kim i Seong-Gook Kang. "Anti-oxidant and Anti-skin-aging Effects of Abalone Viscera Extracts in Human Dermal Fibroblasts". Korean Journal of Food Preservation 19, nr 4 (30.08.2012): 463–69. http://dx.doi.org/10.11002/kjfp.2012.19.4.463.

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Smith, T. J., R. J. Kottke, H. Lum i T. T. Andersen. "Human orbital fibroblasts in culture bind and respond to endothelin". American Journal of Physiology-Cell Physiology 265, nr 1 (1.07.1993): C138—C142. http://dx.doi.org/10.1152/ajpcell.1993.265.1.c138.

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Human fibroblasts in primary cell culture were studied for their ability to bind to endothelin (ET), a 21-amino acid peptide with profound vasoconstricting properties. When 125I-labeled ET-1 was incubated with confluent orbital fibroblasts in the presence of increasing concentrations of unlabeled ligand, a single class of binding site was defined with a dissociation constant of 1.42 x 10(-8) M and a maximal binding capacity of 9.1 x 10(-10) mol/micrograms protein. ET-3 was a substantially less potent competitor for 125I-ET-1 binding sites than was unlabeled ET-1. Dermal fibroblasts demonstrated approximately 75% less ET-1 saturation binding activity, on a cellular protein basis, than did those from the orbit. Orbital fibroblasts responded to ET-1 (10(-9) M) with a rapid and transient increase in the free concentration of intracellular Ca2+ ([Ca2+]i) as assessed by monitoring acetoxymethyl ester of fura 2 fluorescence intensity. Rechallenge with the peptide elicited a substantially attenuated response than that seen after the initial treatment. There was no consistent effect of ET-1 on [Ca2+]i in dermal cultures. ET-3 failed to influence [Ca2+]i in either type of fibroblast. It would appear that orbital fibroblasts bind and respond to ET in a manner distinct from that observed in dermal fibroblasts, raising the possibility that the peptide may have site-specific actions in orbital connective tissue.

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Rodrigues, Annelissa Zorzeto, Paulo Tambasco de Oliveira, Arthur Belém Novaes Jr., Luciana Prado Maia, Sérgio Luís Scombatti de Souza i Daniela Bazan Palioto. "Evaluation of in vitro human gingival fibroblast seeding on acellular dermal matrix". Brazilian Dental Journal 21, nr 3 (2010): 179–89. http://dx.doi.org/10.1590/s0103-64402010000300001.

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The acellular dermal matrix (ADM) was introduced in periodontology as a substitute for the autogenous grafts, which became restricted because of the limited source of donor's tissue. The aim of this study was to investigate, in vitro, the distribution, proliferation and viability of human gingival fibroblasts seeded onto ADM. ADM was seeded with human gingival fibroblasts for up to 21 days. The following parameters were evaluated: cell distribution, proliferation and viability. Results revealed that, at day 7, fibroblasts were adherent and spread on ADM surface, and were unevenly distributed, forming a discontinuous single cell layer; at day 14, a confluent fibroblastic monolayer lining ADM surface was noticed. At day 21, the cell monolayer exhibited a reduction in cell density. At 7 days, about to 90% of adherent cells on ADM surface were cycling while at 14 and 21 days this proportion was significantly reduced. A high proportion of viable cell was detected on AMD surface both on 14 and 21 days. The results suggest that fibroblast seeding onto ADM for 14 days can allow good conditions for cell adhesion and spreading on the matrix; however, migration inside the matrix was limited.

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Worrell, Julie C., Jack Leslie, Graham R. Smith, Marco Y. W. Zaki, Hannah L. Paish, Amber Knox, Michelle L. James i in. "cRel expression regulates distinct transcriptional and functional profiles driving fibroblast matrix production in systemic sclerosis". Rheumatology 59, nr 12 (28.07.2020): 3939–51. http://dx.doi.org/10.1093/rheumatology/keaa272.

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Abstract Objectives NF-κB regulates genes that control inflammation, cell proliferation, differentiation and survival. Dysregulated NF-κB signalling alters normal skin physiology and deletion of cRel limits bleomycin-induced skin fibrosis. This study investigates the role of cRel in modulating fibroblast phenotype in the context of SSc. Methods Fibrosis was assessed histologically in mice challenged with bleomycin to induce lung or skin fibrosis. RNA sequencing and pathway analysis was performed on wild type and Rel−/− murine lung and dermal fibroblasts. Functional assays examined fibroblast proliferation, migration and matrix production. cRel overexpression was investigated in human dermal fibroblasts. cRel immunostaining was performed on lung and skin tissue sections from SSc patients and non-fibrotic controls. Results cRel expression was elevated in murine lung and skin fibrosis models. Rel−/− mice were protected from developing pulmonary fibrosis. Soluble collagen production was significantly decreased in fibroblasts lacking cRel while proliferation and migration of these cells was significantly increased. cRel regulates genes involved in extracellular structure and matrix organization. Positive cRel staining was observed in fibroblasts in human SSc skin and lung tissue. Overexpression of constitutively active cRel in human dermal fibroblasts increased expression of matrix genes. An NF-κB gene signature was identified in diffuse SSc skin and nuclear cRel expression was elevated in SSc skin fibroblasts. Conclusion cRel regulates a pro-fibrogenic transcriptional programme in fibroblasts that may contribute to disease pathology. Targeting cRel signalling in fibroblasts of SSc patients could provide a novel therapeutic avenue to limit scar formation in this disease.

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Kálmán, S., K. A. Garbett, Z. Janka i K. Mirnics. "Human dermal fibroblasts in psychiatry research". Neuroscience 320 (kwiecień 2016): 105–21. http://dx.doi.org/10.1016/j.neuroscience.2016.01.067.

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Deshpande, Manisha, Shabari Tipnis, Prathibha Shetty, Deepa Ghosh, Chandra Viswanathan i Anish Sen Majumdar. "Immunologic properties of human dermal fibroblasts". Human Immunology 71, nr 11 (listopad 2010): 1089–98. http://dx.doi.org/10.1016/j.humimm.2010.08.003.

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Liu, De Wu, Xiang Hu, De Ming Liu i Ping Zou. "Inhibitory Effect of Tetrandrine on the Proliferation of Human Dermal Fibroblasts Derived from Hypertrophic Scars". Advanced Materials Research 268-270 (lipiec 2011): 838–40. http://dx.doi.org/10.4028/www.scientific.net/amr.268-270.838.

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Tetrandrine can inhibit the proliferation and collagen synthesis of fibroblasts in lung and liver tissue confirmed by a series of clinical research. In this chapter, we investigated the effect of Tetrandrine on the proliferation of human dermal fibroblasts derived from hypertrophic scars. The dermal fibroblasts were isolated from human hypertrophic scar tissues and cultured in vitro. Tetrandrine with different concentration were added to culture medium respectively. The proliferative activities were determined. The result show that when the concentration of added Tetrandrine increased from 5μg/ml to 80μg/ml, the proliferative activities of cultured dermal fibroblasts were decreased gradually in dose-dependent manner. It conclusions that Tetrandrine can obviously inhibit the proliferation of human dermal fibroblasts derived from hypertrophic scars.

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Kolsanov, AV V., AN N. Nikolaenko, VV V. Ivanov, SA A. Prikhodko i PV V. Platonov. "DETERMINATION OF BIOCOMPATIBILITY AND CYTOTOXICITY OF POROUS TITANIUM-BASED MATERIALS IN EXPERIMENT". Science and Innovations in Medicine 2, nr 3 (15.09.2017): 18–22. http://dx.doi.org/10.35693/2500-1388-2017-0-3-18-22.

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Aim - to evaluate the proliferative activity of dermal fibroblast cultures in the presence of composite materials based on titanium silicides in vitro. Materials and methods. To assess the proliferative activity of dermal fibroblasts in vitro, the following materials were used: titanium silicide, titanium carbosilicide oxidized in vacuum and without vacuum, titanium VT-00 (comparison group). Testing of proliferative activity was carried out by the direct contact method. The proliferation index, the doubling time and the number of culture doubling during the cultivation period were calculated. Attachment of dermal fibroblasts to the surface of the test materials and their presence on it during cultivation was assessed by scanning electron microscopy. Results. The study of the morphofunctional characteristics of dermal fibroblasts cultured in the presence of the test samples of material showed that during the entire experiment no major changes occurred in any of the series, the cells retained the monolayer growth characteristic of fibroblasts, preferably spindleshaped with 2-4 shoots. Moreover, all cultures of dermal fibroblasts underwent the same number of doublings during the experiment and reached saturation density 7 days after sowing, which indicates good proliferative activity of cells in the presence of test materials. The results of scanning electron microscopy demonstrate the high affinity of human dermal fibroblasts for both titanium silicide and titanium carbosilicides. Conclusion. Absence of morphofunctional changes in dermal fibroblasts and active proliferation testify to the absence of cytotoxicity of the investigated alloys, and the ability of cells to adhere to the surface of materials indicates their good biocompatibility.

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Higgins, Gloria C., Yong Wu i Arnold E. Postlethwaite. "Intracellular IL-1 Receptor Antagonist Is Elevated in Human Dermal Fibroblasts That Overexpress Intracellular Precursor IL-1α". Journal of Immunology 163, nr 7 (1.10.1999): 3969–75. http://dx.doi.org/10.4049/jimmunol.163.7.3969.

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Abstract Cultured dermal fibroblasts from systemic sclerosis patients express higher levels of intracellular IL-1α than fibroblasts from healthy controls. In this study, we found that systemic sclerosis dermal fibroblasts also express higher levels of the intracellular isoform of IL-1 receptor antagonist (icIL-1Ra) than normal fibroblasts after stimulation with IL-1β or TNF-α. A possible relationship between elevated precursor IL-1α (preIL-1α) and elevated icIL-1Ra was investigated by transducing normal dermal fibroblasts to overexpress preIL-1α, preIL-1β, or icIL-1Ra. Fibroblasts that overexpressed icIL-1Ra did not have elevated levels of IL-1α. On the other hand, fibroblasts that overexpressed preIL-1α had at least 4-fold higher basal levels of icIL-1Ra than control fibroblasts and 4-fold higher levels of icIL-1Ra after induction with IL-1β or TNF-α. Fibroblasts overexpressing preIL-1β did not exhibit elevated icIL-1Ra. The differences in icIL-1Ra protein levels were reflected in differences in mRNA. In contrast, IL-1-stimulated levels of MCP-1 and IL-6 were not different in control and preIL-1α-transduced fibroblasts. Addition of neutralizing anti-IL-1α Abs to fibroblast cultures did not diminish basal or stimulated levels of icIL-1Ra in the preIL-1α-transduced cells, supporting an intracellular site of action of preIL-1α. This is the first report of an association between intracellular levels of these IL-1 family members. We hypothesize that intracellular preIL-1α participates in the regulation of icIL-1Ra.

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Hassan, Muhammad Najib Fathi Bin, Zheng Yie Yap, Yee Loong Tang, Min Hwei Ng i Jia Xian Law. "Expired Platelet Concentrate as a Source of Human Platelet Lysate for Xenogeneic-Free Culture of Human Dermal Fibroblasts". Sains Malaysiana 50, nr 8 (31.08.2021): 2355–65. http://dx.doi.org/10.17576/jsm-2021-5008-18.

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Dermal fibroblasts have been used clinically to promote wound healing and to reduce wrinkles. Most of the time, fetal bovine serum (FBS) is used for the expansion of fibroblasts. In addition, chemically defined medium can also be used for fibroblast expansion. Nonetheless, both FBS and chemically defined medium are not ideal to culture cells that will be used clinically as FBS has the risk of pathogen transmission and induction of xenogeneic immune response whilst chemically defined medium is extremely expensive. In this study, we examine the potential of using human platelet lysate (hPL) prepared from expired platelet concentrates to culture human dermal fibroblasts. For the experiments, fibroblasts were cultured with 5 and 10% hPL, with 10% FBS as the control group to compare the cell morphology, viability, growth rate, extracellular matrix gene expression and wound healing. Results showed that fibroblasts cultured with hPL were more elongated and smaller in size. The cell viability was higher than 90% for all groups. Expansion with 10% hPL significantly shorten the population doubling time compared to the 5% hPL and 10% FBS groups. However, fibroblasts cultured with hPL have lower expression of type I collagen, type III collagen and fibronection as well as slower wound closure. In summary, hPL has the potential to be used as a serum substitute for FBS to expand fibroblasts as it significantly increases the cell proliferation. However, further studies are required to determine if the changes in the ECM gene expression and migration of the hPL-expanded fibroblasts will affect the efficacy of the cells in promoting in vivo wound healing.

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Chang, Yu-Ling, Krishna Sriram, Zhenping Wang, Satomi Igawa, Chia-Chi Wu, Paul Insel i Anna Di Nardo. "Dermal Fibroblasts Control Mast Cell reactivity to commensal bacteria". Journal of Immunology 202, nr 1_Supplement (1.05.2019): 122.15. http://dx.doi.org/10.4049/jimmunol.202.supp.122.15.

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Abstract Background Our data suggests, and current literature supports, that when mast cells (MCs) leave the blood and interact with dermal fibroblasts (DFs), they assume a bacterial tolerant phenotype in order to prevent unnecessary inflammation during the encounter with the beneficial commensal microbiome. We hypothesize that the mechanisms that induce the MC tolerant phenotype in human skin is due to dermal fibroblasts interactions. Methods We mimicked the “in vivo” setting by conditioning human cord blood MC (hMC) with human dermal fibroblast (hDF) and, then exposed them to commensal bacteria supernatant. Human MC transcriptome data from the RNA-seq FANTOM5 data collection on MCs freshly isolated from human skin (FANTOM5 study Motakis_et_al_2013) was used to investigate the innate immune phenotype of MCs in the skin. We determined the genes that make hDFs unique by comparing their gene expression profiles with lung and cardiac fibroblasts using RNA-seq analysis and challenged hMCs with the products of these genes. Results We have discovered that hDF conditioned with hMCs, show a decreased expression of interleukins upon commensal stimulation; specifically, multiple cytokines/chemokine such as pro-inflammatory cytokine GM-SCF, IL-8, MCP-1 and anti-inflammatory cytokines IL-10, IL-13 are down-regulated by at least 95% and these cytokines can be controlled by the product of hDF unique genes. Conclusion The human dermal MC reactivity is controlled by hDF’s unique genes that play an important role in regulating the hMC NF-Kb pathway.

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Brown Lobbins, Monica L., Andrzej T. Slominski, Karen A. Hasty, Sicheng Zhang, Duane D. Miller, Wei Li, Tae-Kang Kim i in. "Modulation by 17,20S(OH)2pD of Fibrosis-Related Mediators in Dermal Fibroblast Lines from Healthy Donors and from Patients with Systemic Sclerosis". International Journal of Molecular Sciences 23, nr 1 (29.12.2021): 367. http://dx.doi.org/10.3390/ijms23010367.

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We previously demonstrated that the non-calcemic pregnacalciferol (pD) analog 17,20S (OH)2pD suppressed TGF-β1-induced type I collagen production in cultured normal human dermal fibroblasts. In the present studies, we examined fibroblasts cultured from the lesional skin of patients with systemic sclerosis (scleroderma (SSc)) and assessed the effects of 17,20S(OH)2pD on fibrosis-related mediators. Dermal fibroblast lines were established from skin biopsies from patients with SSc and healthy controls. Fibroblasts were cultured with either 17,20S(OH)2pD or 1,25(OH)2D3 (positive control) with/without TGF-β1 stimulation and extracted for protein and/or mRNA for collagen synthesis and mediators of fibrosis (MMP-1, TIMP-1, PAI-1, BMP-7, PGES, GLI1, and GLI2). 1 7,20S(OH)2pD (similar to 1,25(OH)2D3) significantly suppressed net total collagen production in TGF-β1-stimulated normal donor fibroblast cultures and in cultures of SSc dermal fibroblasts. 17,20S(OH)2pD (similar to 1,25(OH)2D3) also increased MMP-1, BMP-7, and PGES and decreased TIMP-1 and PAI1 expression in SSc fibroblasts. Although 17,20S(OH)2pD had no effect on Gli1 or Gli2 in SSc fibroblasts, it increased Gli2 expression when cultured with TGF-β1 in normal fibroblasts. These studies demonstrated that 17,20S(OH)2pD modulates mediators of fibrosis to favor the reduction of fibrosis and may offer new noncalcemic secosteroidal therapeutic approaches for treating SSc and fibrosis.

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Smith, T. J., H. S. Wang i C. H. Evans. "Leukoregulin is a potent inducer of hyaluronan synthesis in cultured human orbital fibroblasts". American Journal of Physiology-Cell Physiology 268, nr 2 (1.02.1995): C382—C388. http://dx.doi.org/10.1152/ajpcell.1995.268.2.c382.

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Leukoregulin, a 50-kDa glycoprotein lymphokine, can regulate the extracellular matrix in dermal fibroblasts. Here we investigate the effects of leukoregulin on the synthesis of glycosaminoglycans in human orbital fibroblasts. We demonstrate that leukoregulin enhances the incorporation of [3H]glucosamine into glycosaminoglycans. The effect is dose dependent in the concentration range tested (0.1-2 U/ml), is maximal at 1 U/ml, and is time dependent. [3H]glycosaminoglycan accumulation is enhanced 7.67 +/- 1.23-fold (SE, n = 7) in orbital fibroblast strains. Pulse-chase studies indicate that this enhanced accumulation is not a result of a decreased rate of macromolecular degradation. Radiolabeled material induced by leukoregulin is sensitive to Streptomyces hyaluronidase digestion. Dexamethasone (10(-8) M) and cycloheximide (10 micrograms/ml) can block the cytokine's stimulation of hyaluronan synthesis. [35S]sulfate incorporation into glycosaminoglycan is unaffected by leukoregulin. In dermal fibroblasts, leukoregulin increased hyaluronan synthesis 3.66 +/- 0.37-fold (n = 5 strains, P < 0.02 compared with orbit). The increase in hyaluronan synthesis in orbital fibroblasts is substantially greater than that observed previously with other cytokines, making leukoregulin a candidate molecular trigger in Graves' ophthalmopathy.

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Peterson, Joshua M., Jayson W. Jay, Ye Wang, Alejandro A. Joglar, Anesh Prasai, Alen Palackic, Steven E. Wolf i Amina El Ayadi. "Galunisertib Exerts Antifibrotic Effects on TGF-β-Induced Fibroproliferative Dermal Fibroblasts". International Journal of Molecular Sciences 23, nr 12 (15.06.2022): 6689. http://dx.doi.org/10.3390/ijms23126689.

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Dermal fibroblasts in pathological scars secrete constitutively elevated levels of TGF-β, signaling the transcription of fibrotic genes via activin-like kinase 5 (ALK5). In the present study, we examine the antifibrotic effects of galunisertib, a small-molecule inhibitor of ALK5, on fibroproliferative dermal fibroblasts in an in vitro model of wound healing. We induced fibrosis in human dermal fibroblasts with exogenous TGF-β and performed cellular proliferation assays after treatment with varying concentrations of galunisertib. Dermal fibroblast proliferation was diminished to homeostatic levels without cytotoxicity at concentrations as high as 10 μM. An in vitro scratch assay revealed that galunisertib significantly enhanced cellular migration and in vitro wound closure beginning 24 h post-injury. A gene expression analysis demonstrated a significant attenuation of fibrotic gene expression, including collagen-1a, alpha-smooth muscle actin, fibronectin, and connective tissue growth factor, with increased expression of the antifibrotic genes MMP1 and decorin. Protein synthesis assays confirmed drug activity and corroborated the transcription findings. In summary, galunisertib simultaneously exerts antifibrotic effects on dermal fibroblasts while enhancing rates of in vitro wound closure. Galunisertib has already completed phase II clinical trials for cancer therapy with minimal adverse effects and is a promising candidate for the treatment and prevention of pathological cutaneous scars.

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Meewes, C., A. Poswig, J. Dissemond, P. Brenneisen i K. Scharffetter-Kochanek. "Adaptive antioxidant defence in human dermal fibroblasts". British Journal of Dermatology 143, nr 3 (wrzesień 2000): 662–63. http://dx.doi.org/10.1111/j.1365-2133.2000.03740.x.

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Lee, Ling-Yi, i Sheng-Xiu Liu. "Pathogenesis of Photoaging in Human Dermal Fibroblasts". International Journal of Dermatology and Venereology 3, nr 1 (marzec 2020): 37–42. http://dx.doi.org/10.1097/jd9.0000000000000068.

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Coulomb, Bernard, Corinne Lebreton i Louis Dubertret. "Influence of Human Dermal Fibroblasts on Epidermalization". Journal of Investigative Dermatology 92, nr 1 (styczeń 1989): 122–25. http://dx.doi.org/10.1111/1523-1747.ep13071335.

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Slominski, Andrzej, Blazej Zbytek, Andrzej Szczesniewski i Jacobo Wortsman. "Cultured Human Dermal Fibroblasts do Produce Cortisol". Journal of Investigative Dermatology 126, nr 5 (maj 2006): 1177–78. http://dx.doi.org/10.1038/sj.jid.5700204.

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Müller, Kai M., Matthias Bickel, Ueli N. Wiesmann i Bernhard Spörri. "NATURAL KILLER CELLS ACTIVATE HUMAN DERMAL FIBROBLASTS". Cytokine 12, nr 12 (grudzień 2000): 1755–62. http://dx.doi.org/10.1006/cyto.2000.0787.

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Mahmoud, Nouf N., Lubna M. Al-Kharabsheh, Enam A. Khalil i Rana Abu-Dahab. "Interaction of Gold Nanorods with Human Dermal Fibroblasts: Cytotoxicity, Cellular Uptake, and Wound Healing". Nanomaterials 9, nr 8 (6.08.2019): 1131. http://dx.doi.org/10.3390/nano9081131.

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Herein, the cytotoxicity, cellular uptake and wound healing of human dermal fibroblasts were investigated upon treatment with gold nanorods (GNR) decorated with different ligands. Neutral and cationic poly ethylene glycol (PEG)-decorated GNR demonstrated the least cytotoxicity and cellular internalization, while anionic- and bovine serum albumin (BSA)-coated GNR revealed significant cytotoxicity and cellular uptake into human dermal fibroblasts. The cell scratch test demonstrated that neutral, cationic PEGylated GNR and anionic-decorated GNR have accelerated the wound healing rate in vitro after 24 h of incubation with scratched human dermal fibroblasts compared to control, while there was a drastic retardation of wound healing rate of scratched fibroblasts upon exposure to BSA-GNR accompanied with a significant release of the inflammatory cytokine; interlukin-1β (IL-1β). The cytotoxicity of GNR against the dermal cells and their ability to enhance the wound healing in vitro are greatly linked to their surface modifications.

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Jung, Ji-Yong, Joong Shim, Hyun Choi, Tae Lee i Dong Shin. "Human Dermal Stem/Progenitor Cell-Derived Conditioned Medium Improves Senescent Human Dermal Fibroblasts". International Journal of Molecular Sciences 16, nr 8 (13.08.2015): 19027–39. http://dx.doi.org/10.3390/ijms160819027.

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Buranasudja, Visarut, Chawanphat Muangnoi, Kittipong Sanookpan, Hasseri Halim, Boonchoo Sritularak i Pornchai Rojsitthisak. "Eriodictyol Attenuates H2O2-Induced Oxidative Damage in Human Dermal Fibroblasts through Enhanced Capacity of Antioxidant Machinery". Nutrients 14, nr 12 (20.06.2022): 2553. http://dx.doi.org/10.3390/nu14122553.

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Oxidative stress in dermal fibroblasts is strongly correlated with the aging process of the skin. The application of natural compounds that can increase the ability of dermal fibroblasts to counteract oxidative stress is a promising approach to promote skin health and beauty. Eriodictyol is a flavonoid that exerts several pharmacological actions through its antioxidant properties. However, its protective effects on dermal fibroblasts have not yet been investigated. In this study, we investigated whether eriodictyol protects human dermal fibroblasts (BJ fibroblasts) from the harmful effects of hydrogen peroxide (H2O2). Eriodictyol pretreatment significantly prevented necrotic cell death caused by H2O2 exposure. In addition, the level of 2′,7′-dichloro-dihydro-fluorescein oxidation was decreased, and that of glutathione was maintained, indicating that the beneficial effects of eriodictyol against H2O2 were closely associated with oxidative-stress attenuation. Eriodictyol mediates its antioxidant effects on dermal fibroblasts against H2O2 through (i) the direct neutralization of reactive oxygen species; (ii) the enhancement of the activities of H2O2-detoxifying enzymes, including catalase and glutathione peroxidase; and (iii) the induction of the expressions of catalase and glutathione peroxidase 1 via the activation of the Nrf2 signaling system. These results support the potential application of eriodictyol as an ingredient in skincare products for cosmeceutical and pharmaceutical purposes.

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Woo, Yeon I., Hyun Joo Son, Hye Ryeon Lim, Mi Hee Lee, Hyun Sook Baek, Kazufumi Tsubaki i Jong Chul Park. "Effects Of (1→3), (1→6)-β-D-Glucan Behavior in Human Dermal Fibroblast Cells under Serum Starvation". Key Engineering Materials 342-343 (lipiec 2007): 401–4. http://dx.doi.org/10.4028/www.scientific.net/kem.342-343.401.

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Glucans have been reported to stimulate immunity and to promote wound healing. Adult human dermal fibroblast (aHDF) cultured in serum free (serum-starvation). Proliferation of aHDF was measured at various concentrations of β-glucan by MTT assay, and migration was observed for 36h on microscope. The result of fibroblast bioassay, β-glucan had positive influence. In this study, the direct effects of β-glucan on proliferation and migration of human dermal fibroblasts were examined in vitro. That means β-D-glucan has the effect to enhance proliferation and aHDF migration speed, and has the potential as a wound healing agent.

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Tong, Tao, Jinju Park, Youna Moon, Wesuk Kang i Taesun Park. "α-Ionone Protects Against UVB-Induced Photoaging in Human Dermal Fibroblasts". Molecules 24, nr 9 (9.05.2019): 1804. http://dx.doi.org/10.3390/molecules24091804.

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Ultraviolet (UV) light-induced wrinkle formation is a major dermatological problem and is associated with alteration in collagen. Here, we investigated the potential of α-ionone, a naturally occurring aromatic compound, in regulation of UVB-induced photoaging in human Hs68 dermal fibroblasts and identified the mechanisms involved. We found that in human dermal fibroblasts, α-ionone inhibited UVB-induced loss of collagen. α-Ionone upregulated the molecules participating in the TGF-β–SMAD pathway (TGF-β1, phospho-SMAD2/3, Col1A1, and Col1A2), but downregulated the molecules involved in the MAPK–AP-1 signaling pathway (phospho-p38, phospho-JNK, phospho-ERK, phospho-c-Fos, phospho-c-Jun, MMP1, MMP3, and MMP9), in human dermal fibroblasts. α-Ionone treatment also increased hyaluronic acid contents, and this effect was accompanied by an upregulation of mRNA expression of genes (HAS1 and HAS2) involved in hyaluronic acid synthesis. Thus, α-ionone is effective in the prevention of UVB-induced decrease of collagen and hyaluronic acid in human dermal fibroblasts. We propose that α-ionone may prove beneficial for the prevention of UV-induced wrinkle formation and skin damage.

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Idrees, Ayesha, Valeria Chiono, Gianluca Ciardelli, Siegfried Shah, Richard Viebahn, Xiang Zhang i Jochen Salber. "Validation of in vitro assays in three-dimensional human dermal constructs". International Journal of Artificial Organs 41, nr 11 (29.05.2018): 779–88. http://dx.doi.org/10.1177/0391398818775519.

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Three-dimensional cell culture systems are urgently needed for cytocompatibility testing of biomaterials. This work aimed at the development of three-dimensional in vitro dermal skin models and their optimization for cytocompatibility evaluation. Initially “murine in vitro dermal construct” based on L929 cells was generated, leading to the development of “human in vitro dermal construct” consisting of normal human dermal fibroblasts in rat tail tendon collagen type I. To assess the viability of the cells, different assays CellTiter-Blue®, RealTime-Glo™ MT, and CellTiter-Glo® (Promega) were evaluated to optimize the best-suited assay to the respective cell type and three-dimensional system. Z-stack imaging (Live/Dead and Phalloidin/DAPI-Promokine) was performed to visualize normal human dermal fibroblasts inside matrix revealing filopodia-like morphology and a uniform distribution of normal human dermal fibroblasts in matrix. CellTiter-Glo was found to be the optimal cell viability assay among those analyzed. CellTiter-Blue reagent affected the cell morphology of normal human dermal fibroblasts (unlike L929), suggesting an interference with cell biological activity, resulting in less reliable viability data. On the other hand, RealTime-Glo provided a linear signal only with a very low cell density, which made this assay unsuitable for this system. CellTiter-Glo adapted to three-dimensional dermal construct by optimizing the “shaking time” to enhance the reagent penetration and maximum adenosine triphosphate release, indicating 2.4 times higher viability value by shaking for 60 min than for 5 min. In addition, viability results showed that cells were viable inside the matrix. This model would be further advanced with more layers of skin to make a full thickness model.

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Maeda, Kazuhisa, i Shiori Yoshida. "Involvement of Aquaporin 1 in the Motility and in the Production of Fibrillin 1 and Type I Collagen of Cultured Human Dermal Fibroblasts". Cosmetics 9, nr 6 (10.11.2022): 117. http://dx.doi.org/10.3390/cosmetics9060117.

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Aminocarbonyl proteins increase with age in the dermal layer. Gene Chip analysis of mRNA expression in human dermal fibroblasts cultured on collagen gels treated with glyceraldehyde as an aminocarbonyl protein and on untreated collagen gels showed a decrease in the amount of aquaporin 1 (AQP1) mRNA. In this study, we clarified the involvement of AQP1 in collagen gel contraction and the production of fibrillin 1 and type I collagen in cultured human dermal fibroblasts. In the experiment, AQP1 siRNA was transfected into cultured human dermal fibroblasts to deplete AQP1, and the cell motility and contractile activity of the collagen gel were assessed. The production of fibrillin 1 and type I collagen was also examined by RT–qPCR and antibody staining. AQP1 depletion decreased the collagen gel contractile activity, and both the amount of mRNA and the antibody staining of fibrillin 1 and type I collagen decreased. Furthermore, the depletion of AQP1 reduced the levels of F-actin and phosphorylated myosin light chain 2, suggesting their involvement in reductions of the motility and collagen gel contractile activity of fibroblasts. These findings suggest that AQP1 is an important biomolecule for cell motility in human dermal fibroblasts and that decreased motility results in decreased expression of extracellular matrix proteins such as fibrillin 1 and type I collagen.

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Muchkaeva, I. A., E. B. Dashinimaev, A. S. Artyuhov, E. P. Myagkova, E. A. Vorotelyak, Y. Y. Yegorov, K. S. Vishnyakova i in. "Generation of iPS Cells from Human Hair Follice Dermal Papilla Cells". Acta Naturae 6, nr 1 (15.03.2014): 45–53. http://dx.doi.org/10.32607/20758251-2014-6-1-45-53.

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Dermal papilla (DP) cells are unique regional stem cells of the skin that induce formation of a hair follicle and its regeneration cycle. DP are multipotent stem cells; therefore we supposed that the efficiency of DPC reprogramming could exceed that of dermal fibroblasts reprogramming. We generated induced pluripotent stem cells from human DP cells using lentiviral transfection with Oct4, Sox2, Klf4, and c-Myc, and cultivation of cells both in a medium supplemented with valproic acid and at a physiological level of oxygen (5%). The efficiency of DP cells reprogramming was ~0.03%, while the efficiency of dermal fibroblast reprogramming under the same conditions was ~0.01%. Therefore, we demonstrated the suitability of DP cells as an alternative source of iPS cells.

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Hong, L., i J. J. Mao. "Tissue-engineered Rabbit Cranial Suture from Autologous Fibroblasts and BMP2". Journal of Dental Research 83, nr 10 (październik 2004): 751–56. http://dx.doi.org/10.1177/154405910408301003.

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Craniosynostosis is a congenital disorder of premature ossification of cranial sutures, occurring in one of approximately every 2500 live human births. This work addressed a hypothesis that a cranial suture can be tissue-engineered from autologous cells. Dermal fibroblasts were isolated subcutaneously from growing rabbits, culture-expanded, and seeded in a gelatin scaffold. We fabricated a composite tissue construct by sandwiching the fibroblast-seeded gelatin scaffold between two collagen sponges loaded with recombinant human BMP2. Surgically created, full-thickness parietal defects were filled with the composite tissue construct in the same rabbits from which dermal fibroblasts had been obtained. After four-week in vivo implantation, there was de novo formation of tissue-engineered cranial suture, microscopically reminiscent of the adjacent natural cranial suture. The tissue-engineered cranial suture showed radiolucency on radiographic images, in contrast to radio-opacity of microscopically ossified calvarial defects filled with fibroblast-free, BMP2-loaded constructs. This approach may be refined for tissue engineering of cranial sutures for craniosynostosis patients.

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Piela-Smith, T. H., G. Broketa, A. Hand i J. H. Korn. "Regulation of ICAM-1 expression and function in human dermal fibroblasts by IL-4." Journal of Immunology 148, nr 5 (1.03.1992): 1375–81. http://dx.doi.org/10.4049/jimmunol.148.5.1375.

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Abstract ICAM-1 is found on the surface of many hematopoietic and nonhematopoietic cells and can function as an adhesive ligand for the integrin, leukocyte function-associated molecule-1 (LFA-1, CD11a/CD18). ICAM-1/leukocyte function-associated molecule-1 interaction has been shown to be of importance in many immune-mediated cell-cell adhesion reactions. In vitro, unstimulated human fibroblast cell cultures express low levels of ICAM-1. Using ELISA, cytofluorography, electron microscopy, Northern analysis, and an in vitro cell adherence assay, we demonstrate that treatment of human dermal fibroblasts with the cytokine IL-4 leads to an increase in cell surface ICAM-1 expression that is under transcriptional control as well as increased fibroblast adhesion to LFA-1-bearing T lymphocytes. The kinetics of increased ICAM-1 expression induced by IL-4 paralleled the increase in ICAM-1-dependent T lymphocyte adhesion. The increase in T cell adhesion was determined to be due to the effects of IL-4 on the fibroblasts and not the adhering T cells. Treatment of fibroblasts with IL-4 also resulted in enhanced binding of human rhinovirus, a recently reported additional ligand for ICAM-1. Virus binding was IL-4 dose dependent and could be inhibited with mAb to ICAM-1. Both the expression of ICAM-1 and the ICAM-1-dependent increase in T lymphocyte adhesion that was induced by IL-4 could be inhibited by preexposure of the fibroblasts to either IL-1 or IL-6, suggesting that multiple cytokines can have both positive and negative effects on human fibroblast ICAM-1 expression and function.

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Kamalov, Almaz, Mikhail Shishov, Natalia Smirnova, Vera Kodolova-Chukhontseva, Irina Dobrovol’skaya, Konstantin Kolbe, Andrei Didenko, Elena Ivan’kova, Vladimir Yudin i Pierfrancesco Morganti. "Influence of Electric Field on Proliferation Activity of Human Dermal Fibroblasts". Journal of Functional Biomaterials 13, nr 3 (29.06.2022): 89. http://dx.doi.org/10.3390/jfb13030089.

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In this work, an electrically conductive composite based on thermoplastic polyimide and graphene was obtained and used as a bioelectrode for electrical stimulation of human dermal fibroblasts. The values of the electrical conductivity of the obtained composite films varied from 10−15 to 102 S/m with increasing graphene content (from 0 to 5.0 wt.%). The characteristics of ionic and electronic currents flowing through the matrix with the superposition of cyclic potentials ± 100 mV were studied. The high stability of the composite was established during prolonged cycling (130 h) in an electric field with a frequency of 0.016 Hz. It was established that the composite films based on polyimide and graphene have good biocompatibility and are not toxic to fibroblast cells. It was shown that preliminary electrical stimulation increases the proliferative activity of human dermal fibroblasts in comparison with intact cells. It is revealed that an electric field with a strength E = 0.02–0.04 V/m applied to the polyimide films containing 0.5–3.0 wt.% of the graphene nanoparticles activates cellular processes (adhesion, proliferation).

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Germain, Lucie, Andreá Jean, François A. Auger i Dominique R. Garrel. "Human Wound Healing Fibroblasts Have Greater Contractile Properties Than Dermal Fibroblasts". Journal of Surgical Research 57, nr 2 (sierpień 1994): 268–73. http://dx.doi.org/10.1006/jsre.1994.1143.

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Ahuja, Akshay Kumar, Luca Pontiggia, Ueli Moehrlen i Thomas Biedermann. "The Dynamic Nature of Human Dermal Fibroblasts Is Defined by Marked Variation in the Gene Expression of Specific Cytoskeletal Markers". Life 12, nr 7 (22.06.2022): 935. http://dx.doi.org/10.3390/life12070935.

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The evidence for fibroblast heterogeneity is continuously increasing, and recent work has shed some light on the existence of different sub-populations of fibroblasts in the human skin. Although we now have a more precise understanding of their distribution in the human body, we do not know whether their properties are predictive of where these cells derive from or whether these sub-types have functional consequences. In this study, we employed single-cell transcriptomics (10X Genomics) to study gene expression and segregate fibroblast sub-populations based on their genetic signature. We report the differential expression of a defined set of genes in fibroblasts from human skin, which may contribute to their dynamicity in vivo and in vitro. We show that the sub-population of fibroblasts expressing cytoskeletal markers, such as ANXA2, VIM, ACTB, are enriched in an adult skin sample. Interestingly, this sub-population of fibroblasts is not enriched in a neonatal skin sample but becomes predominant when neonatal fibroblasts are cultivated. On the other hand, the fibroblast sub-populations expressing COL1A1 and ELN are enriched in neonatal skin but are reduced in the adult skin and in fibroblasts from neonatal skin that are cultured in vitro. Our results indicate that fibroblasts are a dynamic cell type, and while their genetic make-up changes markedly, only a handful of genes belonging to the same functional pathway govern this alteration. The gene expression pattern of cytoskeletal markers may help in identifying whether the fibroblasts were isolated from an adult or an infant or whether they were cultivated, and this information could be useful for quality control in clinics and in cell banking. Furthermore, this study opens additional avenues to investigate the role of these markers in defining the complexity of human dermal fibroblasts.

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Bae, Ji-Eun, Daejin Min, Ji Yeon Choi, Hyunjung Choi, Joon Bum Kim, Na Yeon Park, Doo Sin Jo i in. "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". International Journal of Molecular Sciences 22, nr 20 (10.10.2021): 10941. http://dx.doi.org/10.3390/ijms222010941.

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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.

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Umetsu, D. T., D. Katzen, H. H. Jabara i R. S. Geha. "Antigen presentation by human dermal fibroblasts: activation of resting T lymphocytes." Journal of Immunology 136, nr 2 (15.01.1986): 440–45. http://dx.doi.org/10.4049/jimmunol.136.2.440.

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Abstract We have shown that human dermal fibroblasts, exposed to interferon-gamma (IFN-gamma) to induce surface class II major histocompatibility complex (MHC) antigens, were capable of presenting tetanus toxoid (TT) antigen to human TT-specific T cell clones. Antigen presentation by fibroblasts was antigen dependent, required HLA-DR expression by fibroblasts, and was MHC restricted. In contrast, we now report that IFN-gamma-treated fibroblasts are unable to present TT antigen to purified resting T cells obtained from the peripheral blood of TT-immune donors. In addition, although IFN-gamma-treated fibroblasts were able to stimulate alloreactive T cell clones, they were unable by themselves to stimulate primary allogeneic responses in resting T cells. The failure of fibroblasts to stimulate resting T cells was not due to suppressor effects by fibroblasts, because induction of TT and alloantigen responses in resting T cells by monocytes was not inhibited by the presence of fibroblasts. On the contrary, IFN-treated fibroblasts were synergistic with small numbers of monocytes in activating resting T cells. In addition, the failure of antigen presentation by fibroblasts to resting T cells was reversed by the addition of recombinant human interleukin 2 (rIL 2) to cultures, but not of purified human interleukin 1 (IL 1). These results emphasize that the requirements for activation of resting T cells differ from those of T cell clones. Although fibroblasts can efficiently present antigen to T cell clones, antigen presentation by fibroblasts to resting T cells requires the addition of exogenous IL 2. It is postulated that fibroblasts differ from classical antigen-presenting cells in that fibroblasts are incapable of stimulating the production of IL 2 in resting T cells.

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Wu, X., B. Ming i L. Dong. "SAT0294 IL33 ACTIVATES FIBROBLASTS AND INDUCES SKIN FIBROSIS IN SYSTEMIC SCLEROSIS". Annals of the Rheumatic Diseases 79, Suppl 1 (czerwiec 2020): 1091.1–1092. http://dx.doi.org/10.1136/annrheumdis-2020-eular.4329.

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Background:Systemic sclerosis (SSc) is a chronic immune-mediated autoimmune disease that is characterized by fibrotic changes of the skin and internal organs, which in turn leads to distortion of tissue structure and gradual loss of organ function. So far, there is still no treatment allows full recovery from this severe disorder. Therefore, it is of great social significance to study the pathogenesis of this disease and find new targets for treatment. Interleukin 33 (IL-33), which is a potent inducer of type 2 immune response, has been confirmed to be involved in the development and progression of multiple fibrotic diseases. However, the role and mechanism of IL-33 in SSc-related fibrosis remains unclear.Objectives:To clarify the role of interleukin 33 (IL-33) and its receptor Suppression of tumorigenicity 2 (ST2) in the skin fibrosis of SSc, so to provides a new target for the treatment of fibrosis in patients with SSc.Methods:The levels of IL-33 and ST2 was analysed in human samples, murine models of SSc and in cultured fibroblasts by immunohistochemistry and immunofluorescence. The functional role of IL-33 was evaluated by detecting changes in proliferation, migration, and activation of fibroblasts stimulated with recombinant IL-33 protein. MAPK and NF-κB signallings of fibroblasts were assessed by western blotting and analyses of target genes. The role of IL-33 in skin fibrosis was analysed in IL-33 deficient mice (il33−/−) and wild-type controls injected with bleomycin or NaCl.Results:The expression of IL-33 and its receptor ST2 were up-regulated in skin lesions of SSc patients (Fig 1 A-C) and bleomycin-treated mice(Fig1 D-F). Compared to the healthy skin, the skin from SSc patients expressed more ST2 on fibroblasts membrane(Fig 1 B-C). IL33 induces MAPK and IκBα activation in human dermal fibroblast(Fig 2 A), and promote proliferation, migration and production of collagen of human dermal fibroblasts, but not the release of inflammatory factors(IL-6, MCP-1)(Fig2 B-G). Mice deficient for IL33 are protected from bleomycin-induced dermal fibrosis (Fig3).Fig 1.Increased expression of IL33, ST2 in SSc patients and bleomycin-treated mice.Fig 2.IL33 induces MAPK and IκBα activation in human dermal fibroblast, and and promote proliferation, migration and production of collagen of human dermal fibroblasts.Fig 3.Mice deficient for IL33 are protected from bleomycin-induced dermal fibrosis.Conclusion:IL33 promotes skin fibrosis by activating fibroblasts, and IL33/ST2 may be an important target for the treatment of fibrosis in patients with SSc.References:[1]Ingegnoli F, Ughi N, Mihai C. Update on the epidemiology, risk factors, and disease outcomes of systemic sclerosis. Best practice & research. Clinical rheumatology. 2018;32(2):223-240.[2]Schmitz J, Owyang A, Oldham E, et al. IL-33, an interleukin-1-like cytokine that signals via the IL-1 receptor-related protein ST2 and induces T helper type 2-associated cytokines. Immunity. 2005;23(5):479-490.[3]Molofsky AB, Savage AK, Locksley RM. Interleukin-33 in Tissue Homeostasis, Injury, and Inflammation.Immunity.2015;42(6):1005-1019.Disclosure of Interests:None declared

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Mahajan, Avinash S., Venkata S. Arikatla, Anita Thyagarajan, Tetyana Zhelay, Ravi P. Sahu, Michael G. Kemp, Dan F. Spandau i Jeffrey B. Travers. "Creatine and Nicotinamide Prevent Oxidant-Induced Senescence in Human Fibroblasts". Nutrients 13, nr 11 (16.11.2021): 4102. http://dx.doi.org/10.3390/nu13114102.

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Dermal fibroblasts provide structural support by producing collagen and other structural/support proteins beneath the epidermis. Fibroblasts also produce insulin-like growth factor-1 (IGF-1), which binds to the IGF-1 receptors (IGF-1Rs) on keratinocytes to activate signaling pathways that regulate cell proliferation and cellular responses to genotoxic stressors like ultraviolet B radiation. Our group has determined that the lack of IGF-1 expression due to fibroblast senescence in the dermis of geriatric individuals is correlated with an increased incidence of skin cancer. The present studies tested the hypothesis that pro-energetics creatine monohydrate (Cr) and nicotinamide (NAM) can protect normal dermal human fibroblasts (DHF) against experimentally induced senescence. To that end, we used an experimental model of senescence in which primary DHF are treated with hydrogen peroxide (H2O2) in vitro, with senescence measured by staining for beta-galactosidase activity, p21 protein expression, and senescence associated secretory phenotype cytokine mRNA levels. We also determined the effect of H2O2 on IGF-1 mRNA and protein expression. Our studies indicate that pretreatment with Cr or NAM protects DHF from the H2O2-induced cell senescence. Treatment with pro-energetics post-H2O2 had no effect. Moreover, these agents also inhibited reactive oxygen species generation from H2O2 treatment. These studies suggest a potential strategy for protecting fibroblasts in geriatric skin from undergoing stress-induced senescence, which may maintain IGF-1 levels and therefore limit carcinogenesis in epidermal keratinocytes.

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Nejaddehbashi, Fereshteh, Vahid Bayati, Leila Mashali, Mahmoud Hashemitabar, Mohammadreza Abbaspour, Eskandar Moghimipour i Mahmoud Orazizadeh. "Isolating human dermal fibroblasts using serial explant culture". Stem Cell Investigation 6 (sierpień 2019): 23. http://dx.doi.org/10.21037/sci.2019.08.05.

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Kim, Mi Na, Taek Jong Kwak, Nae Gyu Kang, Sang Hwa Lee, Sun Gyoo Park i Cheon Koo Lee. "The Effect of Photomodulation in Human Dermal Fibroblasts". Journal of the Society of Cosmetic Scientists of Korea 41, nr 4 (30.12.2015): 325–31. http://dx.doi.org/10.15230/scsk.2015.41.4.325.

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Abdullah, Ahmed, Robert L. McCauley i David N. Herndon. "Stimulation of Human Dermal Fibroblasts with Interleukin 2". Journal of Burn Care & Rehabilitation 12, nr 1 (styczeń 1991): 23–25. http://dx.doi.org/10.1097/00004630-199101000-00006.

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Kim, Jung-Ae, Byul-Nim Ahn, Chang-Suk Kong, Sung-Ha Park, Byoung-Jun Park i Se-Kwon Kim. "Antiphotoaging effect of chitooligosaccharides on human dermal fibroblasts". Photodermatology, Photoimmunology & Photomedicine 28, nr 6 (6.11.2012): 299–306. http://dx.doi.org/10.1111/phpp.12004.

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Mochizuki, Mitsuru, Jens-M. Schröder, Enno Christophers i Shoso Yamamoto. "IL-4 Induces Eotaxin in Human Dermal Fibroblasts". International Archives of Allergy and Immunology 120, nr 1 (1999): 19–23. http://dx.doi.org/10.1159/000053587.

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Saito, Shinichi, Yoshiharu Takayama, Koko Mizumachi i Chise Suzuki. "Lactoferrin promotes hyaluronan synthesis in human dermal fibroblasts". Biotechnology Letters 33, nr 1 (5.09.2010): 33–39. http://dx.doi.org/10.1007/s10529-010-0389-3.

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