Synthetic epidermal pentapeptide and related growth regulatory peptides inhibit proliferation and enhance differentiation in primary and regenerating cultures of human epidermal keratinocytes

1990 ◽  
Vol 97 (1) ◽  
pp. 51-58 ◽  
Author(s):  
P.K. Jensen ◽  
K. Elgjo ◽  
O.D. Laerum ◽  
L. Bolund
Keyword(s):  
Primary Cultures ◽  
Mouse Skin ◽  
Regulatory Peptides ◽  
Epidermal Keratinocytes ◽  
Synthetic Analog ◽  
Proliferating Cells ◽  
Human Epidermal Keratinocytes ◽  
Epidermal Pentapeptide

A pentapeptide that inhibits proliferation of mouse epidermal keratinocytes in vivo and in vitro has been purified from mouse skin extracts. In the present study the effect of a synthetic analog of the epidermal pentapeptide on proliferation and differentiation of cultured human epidermal keratinocytes was investigated. In young, rapidly growing primary cultures the pentapeptide caused a dramatic decrease in mitotic activity and also induced pronounced changes in the balance between kinetically defined subpopulations of proliferating cells. A dipeptide derived from the pentapeptide was found to be at least as potent. A serine derivative of a hemoregulatory peptide also seemed to be active. When tested in epidermal cultures regenerating after removal of the suprabasal cell layers, both the pentapeptide and the dipeptide were shown to cause a delay in the proliferative response. Both peptides were also able to stimulate early (increase in cell size) and late (cornified envelope formation) events in the differentiation pathway of the keratinocyte. The apparent stimulatory effect on differentiation was most clearly seen in regenerating cultures, whereas the effect on primary cultures varied with the experimental set-up. It is suggested that homologous epidermal peptide(s) may play a major role in the regulation of human epidermal homeostasis.

scholarly journals 5-Aminolevulinic Acid-Based Photodynamic Therapy Pretreatment Mitigates Ultraviolet A-Induced Oxidative Photodamage

2018 ◽  
Vol 2018 ◽  
pp. 1-11 ◽  
Author(s):  
Hui Hua ◽  
Jiawei Cheng ◽  
Wenbo Bu ◽  
Juan Liu ◽  
Weiwei Ma ◽  
...  
Keyword(s):  
Aminolevulinic Acid ◽  
Epidermal Keratinocytes ◽  
Control Group ◽  
Hacat Cells ◽  
Ultraviolet A ◽  
Hairless Mice ◽  
Human Epidermal Keratinocytes ◽  
Experimental Group

Aim. To determine whether 5-aminolevulinic acid-based photodynamic therapy (ALA-PDT) is effective in combating ultraviolet A- (UVA-) induced oxidative photodamage of hairless mice skin in vivo and human epidermal keratinocytes in vitro. Methods. In in vitro experiments, the human keratinocyte cell line (HaCaT cells) was divided into two groups: the experimental group was treated with ALA-PDT and the control group was left untreated. Then, the experimental group and the control group of cells were exposed to 10 J/m2 of UVA radiation. ROS, O2− species, and MMP were determined by fluorescence microscopy; p53, OGG1, and XPC were determined by Western blot analysis; apoptosis was determined by flow cytometry; and 8-oxo-dG was determined by immunofluorescence. Moreover, HaCaT cells were also treated with ALA-PDT. Then, SOD1 and SOD2 were examined by Western blot analysis. In in vivo experiments, the dorsal skin of hairless mice was treated with ALA-PDT or saline-PDT, and then, they were exposed to 20 J/m2 UVA light. The compound 8-oxo-dG was detected by immunofluorescence. Conclusion. In human epidermal keratinocytes and hairless mice skin, UVA-induced oxidative damage can be prevented effectively with ALA-PDT pretreatment.

scholarly journals Gps2, a Protein Partner for Human Papillomavirus E6 Proteins

2001 ◽  
Vol 75 (1) ◽  
pp. 151-160 ◽  
Author(s):  
Yan Yan Degenhardt ◽  
Saul J. Silverstein
Keyword(s):  
Transcriptional Activation ◽  
Epidermal Keratinocytes ◽  
Human Epidermal Keratinocytes ◽  
Papilloma Virus ◽  
Hpv E6 ◽  
Yeast Two Hybrid System ◽  
Protein Partners ◽  
Normal Human

ABSTRACT We have used the yeast two-hybrid system to screen a cDNA library prepared from normal human epidermal keratinocytes and identified protein partners for human papilloma virus (HPV) E6 proteins. A clone that encoded Gps2 interacted with E6 proteins from HPVs of high and low oncogenic risk. The specificity of these reactions was verified and the regions of E6 that were required for interaction were mapped. Steady-state and pulse-chase analyses of cells cotransfected with DNAs expressing E6 from either HPV6 or HPV18 and Gps2 demonstrated that the E6 proteins induced the degradation of Gps2 in vivo but not in vitro. Gps2 exhibited transcriptional activation activity, and high-risk E6 suppressed this activity.

Comparative Removal of Pyrimidine Dimers from Human Epidermal Keratinocytes In Vivo and In Vitro

1988 ◽  
Vol 91 (4) ◽  
pp. 349-352 ◽  
Author(s):  
Michael K. Reusch ◽  
Kathleen Meager ◽  
Steven A. Leadon ◽  
Philip C. Hanawalt
Keyword(s):  
Epidermal Keratinocytes ◽  
Human Epidermal Keratinocytes ◽  
Pyrimidine Dimers

scholarly journals S100C/A11 is a key mediator of Ca2+-induced growth inhibition of human epidermal keratinocytes

2003 ◽  
Vol 163 (4) ◽  
pp. 825-835 ◽  
Author(s):  
Masakiyo Sakaguchi ◽  
Masahiro Miyazaki ◽  
Mikiro Takaishi ◽  
Yoshihiko Sakaguchi ◽  
Eiichi Makino ◽  
...  
Keyword(s):  
Growth Inhibition ◽  
Growth Regulation ◽  
Nuclear Translocation ◽  
Basal Layer ◽  
Human Keratinocytes ◽  
Negative Regulator ◽  
Epidermal Keratinocytes ◽  
Proliferating Cells ◽  
Human Epidermal Keratinocytes

An increase in extracellular Ca2+ induces growth arrest and differentiation of human keratinocytes in culture. We examined possible involvement of S100C/A11 in this growth regulation. On exposure of the cells to high Ca2+, S100C/A11 was specifically phosphorylated at 10Thr and 94Ser. Phosphorylation facilitated the binding of S100C/A11 to nucleolin, resulting in nuclear translocation of S100C/A11. In nuclei, S100C/A11 liberated Sp1/3 from nucleolin. The resulting free Sp1/3 transcriptionally activated p21CIP1/WAF1, a representative negative regulator of cell growth. Introduction of anti-S100C/A11 antibody into the cells largely abolished the growth inhibition induced by Ca2+ and the induction of p21CIP1/WAF1. In the human epidermis, S100C/A11 was detected in nuclei of differentiating cells in the suprabasal layers, but not in nuclei of proliferating cells in the basal layer. These results indicate that S100C/A11 is a key mediator of the Ca2+-induced growth inhibition of human keratinocytes in culture, and that it may be possibly involved in the growth regulation in vivo as well.

Novel protein in human epidermal keratinocytes: regulation of expression during differentiation

1988 ◽  
Vol 8 (5) ◽  
pp. 2204-2210
Author(s):  
T Kartasova ◽  
G N van Muijen ◽  
H van Pelt-Heerschap ◽  
P van de Putte
Keyword(s):  
Uv Light ◽  
Rabbit Antiserum ◽  
Keratinocyte Differentiation ◽  
Epidermal Keratinocytes ◽  
Cdna Clones ◽  
Regulation Of Expression ◽  
Human Epidermal Keratinocytes

Recently, two groups of cDNA clones have been isolated from human epidermal keratinocytes; the clones correspond to genes whose expression is stimulated by exposure of the cells to UV light or treatment with 4-nitroquinoline 1-oxide or 12-O-tetradecanoylphorbol 13-acetate (T. Kartasova and P. van de Putte, Mol. Cell. Biol. 8:2195-2203, 1988). The proteins predicted by the nucleotide sequence of both groups of cDNAs are small (8 to 10 kilodaltons), are exceptionally rich in proline, glutamine, and cysteine, and contain repeating elements with a common sequence, PK PEPC. These proteins were designated sprI and sprII (small, proline rich). Here we describe the characterization of the sprIa protein, which is encoded by one of the group 1 cDNAs. The expression of this protein during keratinocyte differentiation in vitro and the distribution of the sprIa protein in some human tissues was studied by using a specific rabbit antiserum directed against a synthetic polypeptide corresponding to the 30 amino acids of the C-terminal region of the sprIa gene product. The results indicate that the expression of the sprIa protein is stimulated during keratinocyte differentiation both in vitro and in vivo.

scholarly journals A Novel Substance P-Based Hydrogel for Increased Wound Healing Efficiency

Molecules ◽  
2018 ◽  
Vol 23 (9) ◽  
pp. 2215 ◽  
Author(s):  
Da Kim ◽  
Ji Jang ◽  
Song Jang ◽  
Jungsun Lee
Keyword(s):  
Wound Healing ◽  
Substance P ◽  
Dermal Fibroblasts ◽  
Epidermal Keratinocytes ◽  
Human Epidermal Keratinocytes ◽  
In Vivo Experiments ◽  
And Migration ◽  
Proliferation And Migration

The neuropeptide substance P (SP) is known to stimulate wound healing by regulating the production of relevant cytokines as well as cell proliferation and migration. However, the therapeutic application of SP is limited by its low stability under biological conditions and oxidation during purification, formulation, and storage. To address this problem, we developed a novel formulation of SP as an SP gel, and investigated its wound healing activity both in vitro and in vivo. SP in SP gel was stable at various temperatures for up to 4 weeks. In vitro, SP gel exhibited more potential as a candidate wound-healing agent than SP alone, as evidenced by the observed increases in the proliferation and migration of human epidermal keratinocytes and human dermal fibroblasts. In vivo experiments showed that SP gel treatment enhanced the healing of full-thickness wounds in mice as compared to SP alone. These results demonstrate the benefits of SP gel as a promising topical agent for wound treatment.

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

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

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

In vitro C3 mRNA Expression in Pemphigus Vulgaris: Complement Activation is Increased by IL-1α and TNF-α

1999 ◽  
Vol 3 (3) ◽  
pp. 140-144 ◽  
Author(s):  
Claudio Feliciani ◽  
Paola Toto ◽  
Paolo Amerio ◽  
Pierluigi Amerio
Keyword(s):  
Mrna Expression ◽  
Complement Activation ◽  
In Vitro Study ◽  
Peak Level ◽  
Pemphigus Vulgaris ◽  
Epidermal Keratinocytes ◽  
Human Epidermal Keratinocytes ◽  
Tnf Α

Background: Pemphigus vulgaris (PV) is a potentially life-threatening disease, characterized immunohistologically by IgG deposits and complement activation on the surface of keratinocytes. Complement activation has been implicated in the pathogenesis with C3 deposits in about 90% of patients. Objective: In order to further elucidate the role of complement in PV and to define which cytokines play a role in C3 mRNA expression, we performed an in vitro study in human keratinocytes. Methods: Normal human epidermal keratinocytes (NHuK) were incubated with PV serum and C3 mRNA was measured. We previously had shown that IL-1α and TNF-α are expressed in PV in vivo and in vitro. Since cytokines are able to modulate complement activation, mRNA expression was evaluated in a similar experiment after pretreatment using antibodies against IL-1α and TNF-α. Results: Incubation of NHuK with PV sera caused their detachment from the plates after 20–30 minutes with a complete acantholysis within 12 hours. An early C3 mRNA expression was seen after 30 minutes with a peak level after 1 hour. Blocking studies, using antibodies against human IL-1α and TNF-α in NHuK together with PV-IgG, showed reduction of in vitro induced acantholysis and inhibition of C3 mRNA expression. Conclusions: This study supports the hypothesis that complement C3 is important in PV acantholysis and that complement activation is increased by IL-1α and TNF-α.

scholarly journals Melanogenesis Inhibitors from the Rhizoma of Ligusticum Sinense in B16-F10 Melanoma Cells In Vitro and Zebrafish In Vivo

2018 ◽  
Vol 19 (12) ◽  
pp. 3994 ◽  
Author(s):  
Min-Chi Cheng ◽  
Tzong-Huei Lee ◽  
Yi-Tzu Chu ◽  
Li-Ling Syu ◽  
Su-Jung Hsu ◽  
...  
Keyword(s):  
Epidermal Keratinocytes ◽  
Preparative Hplc ◽  
Active Components ◽  
Human Epidermal Keratinocytes ◽  
Methanolic Extracts ◽  
Whitening Agent ◽  
Ic50 Values ◽  
New Compounds

The rhizoma of Ligusticum sinense, a Chinese medicinal plant, has long been used as a cosmetic for the whitening and hydrating of the skin in ancient China. In order to investigate the antimelanogenic components of the rhizoma of L. sinense, we performed an antimelanogenesis assay-guided purification using semi-preparative HPLC accompanied with spectroscopic analysis to determine the active components. Based on the bioassay-guided method, 24 compounds were isolated and identified from the ethyl acetate layer of methanolic extracts of L. sinense, and among these, 5-[3-(4-hydroxy-3-methoxyphenyl)allyl]ferulic acid (1) and cis-4-pentylcyclohex-3-ene-1,2-diol (2) were new compounds. All the pure isolates were subjected to antimelanogenesis assay using murine melanoma B16-F10 cells. Compound 1 and (3S,3aR)-neocnidilide (8) exhibited antimelanogenesis activities with IC50 values of 78.9 and 31.1 μM, respectively, without obvious cytotoxicity. Further investigation showed that compound 8 demonstrated significant anti-pigmentation activity on zebrafish embryos (10‒20 μM) compared to arbutin (20 μM), and without any cytotoxicity against normal human epidermal keratinocytes. These findings suggest that (3S,3aR)-neocnidilide (8) is a potent antimelanogenic and non-cytotoxic natural compound and may be developed potentially as a skin-whitening agent for cosmetic uses.

scholarly journals Impact of isoflavone genistein on psoriasis in in vivo and in vitro investigations

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Katarzyna Bocheńska ◽  
Marta Moskot ◽  
Elwira Smolińska-Fijołek ◽  
Joanna Jakóbkiewicz-Banecka ◽  
Aneta Szczerkowska-Dobosz ◽  
...  
Keyword(s):  
Mrna Level ◽  
Response Characteristic ◽  
Epidermal Keratinocytes ◽  
Serious Adverse Events ◽  
Human Epidermal Keratinocytes ◽  
Good Tolerability ◽  
Tnf Α ◽  
Pi3k Activation

AbstractGenistein is applied worldwide as an alternative medicament for psoriasis (Ps) because of its anti-inflammatory activity and perceived beneficial impact on the skin. Hereby, we report our in vivo and in vitro investigations to supplement scientific research in this area. The reduction of clinical and biochemical scores in mild to moderate Ps patients taking genistein, its safety, good tolerability with no serious adverse events or discontinuations of treatment, no dose-limiting toxicities, negligible changes in pharmacodynamic parameters and remarkable serum interleukin level alterations were documented in this study. A certain regression of the Ps phenotype was visible, based on photo-documented Ps lesion evaluation. Through in vitro experiments, we found that genistein reduced IL-17A and TNF-α induced MAPK, NF-κB, and PI3K activation in normal human epidermal keratinocytes. Moreover, at the mRNA level of genes associated with the early inflammatory response characteristic for Ps (CAMP, CCL20, DEFB4A, PIK3CA, S100A7, and S100A9) and key cellular signalling (MTORC1 and TFEB), we showed that this isoflavone attenuated the increased response of IL-17A- and TNF-α-related pathways. This allows us to conclude that genistein is a good candidate for Ps treatment, being attractive for co-pharmacotherapy with other drugs.

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