Anti-proliferative effects of an herbal formulated cream on human keratinocytes and its implication for psoriasis treatment

2016 ◽  
Vol 5 (07) ◽  
pp. 4686 ◽  
Author(s):  
Harsha M. R.* ◽  
Baidyanath Mishra ◽  
Chaithra C. S. ◽  
Vivekananda Ramana
Keyword(s):  
Cell Model ◽  
Test Material ◽  
Epidermal Keratinocytes ◽  
Recurrence Rates ◽  
Inflammatory Infiltration ◽  
Keratinocyte Proliferation ◽  
Psoriasis Treatment ◽  
Study Material ◽  
Keratinocyte Cell ◽  
Promising Source

Psoriasis is a chronic inflammatory skin disorder which affects more than 3% of the population worldwide and is characterized histopathologically by proliferative imbalance and abnormal differentiation of epidermal keratinocytes and inflammatory infiltration. Hence, loss of regulation in keratinocyte proliferation and differentiation makes it a typical pathophysiological phenomenon in psoriasis manifestation. Traditionally, herbal products used in treating psoriasis have shown promising effects in several clinical studies with relatively fewer adverse effects, higher remission and lower recurrence rates. In our previous study, the polyherbal formulation of InnoVision’s test material was found to induce AQP-3 expression in keratinocyte cell line. In the present study, we screened the study material for its anti-proliferative properties using cultured human HACAT keratinocyte cell model. Our experimental results suggest that InnoVision’s Psoriderm Cream is a promising source which can be effectively used as an herb-based topical agent for psoriasis treatment. Evidence is provided that inhibition of keratinocyte proliferation and improving skin hydration via induction of aquaporin-3 stimulation is the possible underlying mechanism for the observed anti-psoriatic action of study material. 

scholarly journals Isolation, characterization and evaluation of anti-proliferative properties of andrographolide isolated from Andrographis paniculata on cultured HaCaT cells

2021 ◽  
Vol 67 (1) ◽  
pp. 35-45
Author(s):  
Shammy Jindal ◽  
Rajendra Awasthi ◽  
Dhananjay Singare ◽  
Giriraj T. Kulkarni
Keyword(s):  
Cell Model ◽  
Inhibitory Effect ◽  
Epidermal Keratinocytes ◽  
Herbal Extracts ◽  
Inflammatory Skin Disease ◽  
Inflammatory Infiltration ◽  
Synthetic Drugs ◽  
Significant Inhibitory Effect ◽  
Hacat Keratinocyte ◽  
First Time

Summary Introduction: Psoriasis is an inflammatory skin disease characterized by hyper-proliferation, abnormal epidermal keratinocytes and inflammatory infiltration. It affects approximately 4% of the population globally. Herbal extracts have better results with less toxic effects than the synthetic drugs in the treatment of psoriasis. Objective: Present study was aimed to access the anti-psoriatic effect of andrographolide extracted from Andrographis paniculate (A. paniculata). Method: We extracted, characterized, and screened the extracted andrographolide for anti-proliferative characteristics using cultured cell model of human HaCaT keratinocyte. Results: Andrographolide at 31.25 µg/mL (90 µM) demonstrated significant inhibitory effect on human HaCaT keratinocytes proliferation in cell culture. To our best knowledge, we reported the anti-proliferative potency of andrographolide extracted from A. paniculata for the first time. Conclusion: The results suggest that the andrographolide extracted from A. paniculata plant may have potential to be used in the management of psoriasis.

scholarly journals The endoribonuclease N4BP1 prevents psoriasis by controlling both keratinocytes proliferation and neutrophil infiltration

2021 ◽  
Vol 12 (5) ◽  
Author(s):  
Chenliang Gou ◽  
Wenkai Ni ◽  
Panpan Ma ◽  
Fengbo Zhao ◽  
Zhou Wang ◽  
...  
Keyword(s):  
Physiological Role ◽  
Neutrophil Infiltration ◽  
Proper Function ◽  
Psoriatic Skin ◽  
Epidermal Keratinocytes ◽  
Keratinocyte Proliferation ◽  
Proliferation And Differentiation ◽  
Long Time ◽  
Chronic Skin ◽  
Upregulated Genes

AbstractPsoriasis is a common chronic skin disease, characterized by abnormal interplay between hyperproliferative epidermal keratinocytes and self-reactive immune cells with not fully addressed molecular mechanism. N4BP1 (NEDD4-binding protein 1) is considered as an immune regulator for a long time but its physiological role is not determined yet. Here, we found that the expression of N4BP1 in skin was highest among all 54 tested tissues, and its expression was further upregulated in psoriatic skin. N4BP1-deficient mice exhibited normal grossly, but developed severe and prolonged IMQ-induced psoriasis-like disease comparing to controls. N4BP1 mainly expressed in keratinocytes and located on nucleus. Up- but not downregulated genes in N4BP1-deficient skin were specifically enriched in keratinocyte proliferation and differentiation. The proliferation of N4BP1-deficient primary keratinocytes was faster compared to that of controls. The upregulated genes upon ablation of N4BP1 were highly enriched in targets of AP-1 transcription factor. Knocking out N4BP1 resulted in upregulation of JunB and FosB, and conversely, overexpression of N4BP1 greatly reduced their expression. Furthermore, N4BP1 binds with JunB and FosB encoding mRNAs and greatly reduces their stability. In addition, with a high expression in neutrophils, N4BP1 limits survival of neutrophils in blood and infiltration of neutrophils in psoriatic skin by targeting CXCL1, CCL20, and S100A8. These findings demonstrate that N4BP1 controls the proper function of keratinocytes and neutrophils by negatively regulating JunB, FosB, and CXCL1, respectively, and that is critical for psoriasis prevention.

scholarly journals Apoptosis as a Mechanism for Keratinocyte Death in Canine Toxic Epidermal Necrolysis

2016 ◽  
Vol 54 (2) ◽  
pp. 249-253 ◽  
Author(s):  
F. Banovic ◽  
S. Dunston ◽  
K. E. Linder ◽  
P. Rakich ◽  
T. Olivry
Keyword(s):  
Cell Death ◽  
Toxic Epidermal Necrolysis ◽  
Caspase 3 ◽  
Skin Lesions ◽  
Terminal Deoxynucleotidyl Transferase ◽  
Epidermal Keratinocytes ◽  
Biopsy Specimens ◽  
Significant Difference ◽  
Keratinocyte Cell ◽  
Life Threatening

In humans and dogs, toxic epidermal necrolysis (TEN) is a life-threatening dermatosis characterized by sudden epidermal death resulting in extensive skin detachment. There is little information on the pathogenesis of keratinocyte cell death in canine TEN. We studied the occurrence of apoptosis in skin lesions of dogs with TEN to determine if apoptosis contributes to the pathogenesis of this disease. Immunostaining with antibodies to activated caspase-3 and the terminal deoxynucleotidyl-transferase (TdT)–mediated deoxyuridine triphosphate (dUTP) nick-end labeling technique revealed positive apoptotic keratinocytes in basal and suprabasal epidermal compartments in 17 biopsy specimens collected from 3 dogs with TEN and 16 from 3 dogs with erythema multiforme (EM). There was no significant difference in the number of positively stained epidermal cells between TEN and EM. These results suggest that apoptosis of epidermal keratinocytes and lymphocytic satellitosis represent one of the early steps in the pathogenesis of canine TEN, as in the human disease counterpart.

scholarly journals Mutant p63 affects epidermal cell identity through rewiring the enhancer landscape

2018 ◽  
Author(s):  
Jieqiong Qu ◽  
Sabine Tanis ◽  
Jos P.H. Smits ◽  
Evelyn N. Kouwenhoven ◽  
Martin Oti ◽  
...  
Keyword(s):  
Gene Expression ◽  
Dna Binding ◽  
Epidermal Cell ◽  
Developmental Disorders ◽  
Molecular Mechanisms ◽  
Epidermal Keratinocytes ◽  
Cell Identity ◽  
Keratinocyte Proliferation ◽  
Eec Syndrome ◽  
Proliferation And Differentiation

AbstractTranscription factor p63 is a key regulator of epidermal keratinocyte proliferation and differentiation. In humans mutations in p63 cause several developmental disorders with defects of ectoderm-derived structures including the epidermis. The underlying molecular mechanisms of these mutations however remain unclear. Here we characterized the transcriptome and epigenome from EEC syndrome patients carrying mutations in the p63 DNA-binding domain. The transcriptome of p63 mutant keratinocytes deviated from the normal epidermal cell identity. Epigenomic analyses showed that the deregulated gene expression in p63 mutant keratinocytes resulted from an altered enhancer landscape contributed by loss of p63-bound active enhancers and by unexpected gain of enhancers. The gained enhancers in mutant keratinocytes were frequently bound by deregulated transcription factors such as RUNX1. Reversing RUNX1 overexpression partially rescued deregulated gene expression as well as the enhancer distribution. Our findings support the pivotal role of p63 in controlling the enhancer landscape of epidermal keratinocytes and identify a novel mechanism whereby p63 DNA-binding mutations associated with EEC syndrome rewire the enhancer landscape and affect epidermal cell identity.

Keratinocyte growth regulation in fibroblast cocultures via a double paracrine mechanism

1999 ◽  
Vol 112 (12) ◽  
pp. 1843-1853 ◽  
Author(s):  
N. Maas-Szabowski ◽  
A. Shimotoyodome ◽  
N.E. Fusenig
Keyword(s):  
Neutralizing Antibodies ◽  
Growth Regulation ◽  
Keratinocyte Growth Factor ◽  
Dermal Fibroblasts ◽  
Tissue Homeostasis ◽  
Epidermal Keratinocytes ◽  
Human Epidermal Keratinocytes ◽  
Keratinocyte Proliferation ◽  
Normal Human ◽  
Kinetics Of

Epithelial-mesenchymal interactions play an important role in regulating tissue homeostasis and repair. For skin, the regulatory mechanisms of epidermal-dermal interactions were studied in cocultures of normal human epidermal keratinocytes (NEK) and dermal fibroblasts (HDF) rendered postmitotic by alpha-irradiation (HDFi). The expression kinetics of different cytokines and their receptors with presumed signalling function in skin were determined at the RNA and protein level in mono- and cocultured NEK and HDFi. In cocultured HDFi, mRNA and protein synthesis of keratinocyte growth factor (KGF) (FGF-7) was strongly enhanced, whereas in cocultured keratinocytes interleukin (IL)-1alpha and -1beta mRNA expression increased compared to monocultures. Thus we postulated that IL-1, which had no effect on keratinocyte proliferation, induced in fibroblasts the expression of factors stimulating keratinocyte proliferation, such as KGF. The functional significance of this reciprocal modulation was substantiated by blocking experiments. Both IL-1alpha and -1beta-neutralizing antibodies and IL-1 receptor antagonist significantly reduced keratinocyte proliferation supposedly through abrogation of KGF production, because IL-1 antibodies blocked the induced KGF production. These data indicate a regulation of keratinocyte growth by a double paracrine mechanism through release of IL-1 which induces KGF in cocultured fibroblasts. Thus IL-1, in addition to its proinflammatory function in skin, may play an essential role in regulating tissue homeostasis.

scholarly journals Persea americanaMill. Seed: Fractionation, Characterization, and Effects on Human Keratinocytes and Fibroblasts

2013 ◽  
Vol 2013 ◽  
pp. 1-12 ◽  
Author(s):  
Maria del R. Ramos-Jerz ◽  
Socorro Villanueva ◽  
Gerold Jerz ◽  
Peter Winterhalter ◽  
Alexandra M. Deters
Keyword(s):  
Chlorogenic Acid ◽  
Dermal Fibroblasts ◽  
Persea Americana ◽  
Epidermal Keratinocytes ◽  
Hacat Keratinocytes ◽  
Human Epidermal Keratinocytes ◽  
Residual Solvent ◽  
Keratinocyte Proliferation ◽  
Normal Human

Methanolic avocado (Persea americanaMill., Lauraceae) seed extracts were separated by preparative HSCCC. Partition and HSCCC fractions were principally characterized by LC-ESI-MS/MS analysis. Theirin vitroinfluence was investigated on proliferation, differentiation, cell viability, and gene expression on HaCaT and normal human epidermal keratinocytes (NHEK) and normal human dermal fibroblasts (NHDF). The methanol-water partition (M) from avocado seeds and HSCCC fraction 3 (M.3) were mostly composed of chlorogenic acid and its isomers. Both reduced NHDF but enhanced HaCaT keratinocytes proliferation. HSCCC fractionM.2composed of quinic acid among chlorogenic acid and its isomers inhibited proliferation and directly induced differentiation of keratinocytes as observed on gene and protein level. Furthermore,M.2increased NHDF proliferation via upregulation of growth factor receptors. Salidrosides and ABA derivatives present in HSCCC fractionM.6increased NHDF and keratinocyte proliferation that resulted in differentiation. The residual solvent fractionM.7contained among low concentrations of ABA derivatives high amounts of proanthocyanidins B1 and B2 as well as an A-type trimer and stimulated proliferation of normal cells and inhibited the proliferation of immortalized HaCaT keratinocytes.

Neural Correlates of Retrieval Orientation: Effects of Study–Test Similarity

2004 ◽  
Vol 16 (7) ◽  
pp. 1196-1210 ◽  
Author(s):  
Michael Hornberger ◽  
Alexa M. Morcom ◽  
Michael D. Rugg
Keyword(s):  
Neural Correlates ◽  
Test Material ◽  
Visual Words ◽  
Test Items ◽  
Study Material ◽  
Study Materials ◽  
Orientation Effects ◽  
Retrieval Orientation ◽  
Study Test ◽  
Cue Processing

ERPs elicited by correctly classified unstudied items in tests of yes/no recognition memory were used to investigate the neural correlates of retrieval cue processing. Items in Experiment 1 consisted of pictures and their corresponding names, allowing study and test material to be factorially crossed in four separate study–test cycles. The ERPs elicited by unstudied pictures and words were, in each case, more negative-going when the study material belonged to the alternative rather than the same class of items. These findings demonstrate that previously reported ERP “retrieval orientation effects” depend on differences in similarity between study and test items, and not on the form of the sought for material. In Experiments 2a and 2b, study materials were auditory words and pictures, and the test items were visual words. In both experiments, ERPs elicited by unstudied test words were more negative-going when pictures rather than auditory words were the study material. Thus, ERP retrieval orientation effects do not depend on the employment of a copy cue condition. It is proposed that the effects reflect differences in the processing necessary to maximize over lap between cue and memory representations.

scholarly journals α4/α9 Integrins Coordinate Epithelial Cell Migration Through Local Suppression of MAP Kinase Signaling Pathways

2021 ◽  
Vol 9 ◽  
Author(s):  
Willow Hight-Warburton ◽  
Robert Felix ◽  
Andrew Burton ◽  
Hannah Maple ◽  
Magda S. Chegkazi ◽  
...  
Keyword(s):  
Cell Migration ◽  
Protein Complexes ◽  
Focal Adhesions ◽  
Leading Edge ◽  
Collective Cell Migration ◽  
Keratinocyte Proliferation ◽  
Basal Keratinocytes ◽  
Keratinocyte Cell

Adhesion of basal keratinocytes to the underlying extracellular matrix (ECM) plays a key role in the control of skin homeostasis and response to injury. Integrin receptors indirectly link the ECM to the cell cytoskeleton through large protein complexes called focal adhesions (FA). FA also function as intracellular biochemical signaling platforms to enable cells to respond to changing extracellular cues. The α4β1 and α9β1 integrins are both expressed in basal keratinocytes, share some common ECM ligands, and have been shown to promote wound healing in vitro and in vivo. However, their roles in maintaining epidermal homeostasis and relative contributions to pathological processes in the skin remain unclear. We found that α4β1 and α9β1 occupied distinct regions in monolayers of a basal keratinocyte cell line (NEB-1). During collective cell migration (CCM), α4 and α9 integrins co-localized along the leading edge. Pharmacological inhibition of α4β1 and α9β1 integrins increased keratinocyte proliferation and induced a dramatic change in cytoskeletal remodeling and FA rearrangement, detrimentally affecting CCM. Further analysis revealed that α4β1/α9β1 integrins suppress extracellular signal-regulated kinase (ERK1/2) activity to control migration through the regulation of downstream kinases including Mitogen and Stress Activated Kinase 1 (MSK1). This work demonstrates the roles of α4β1 and α9β1 in regulating migration in response to damage cues.

scholarly journals Canine Epidermal Keratinocytes (CPEK) Grown in Monolayer Are Not Representative of Normal Canine Keratinocytes for Permeability Studies: Pilot Studies

2022 ◽  
Vol 9 (1) ◽  
pp. 25
Author(s):  
Rosanna Marsella ◽  
Rachel Wilkes ◽  
Kim Ahrens
Keyword(s):  
Skin Barrier ◽  
Epidermal Keratinocytes ◽  
Epithelial Permeability ◽  
Electric Resistance ◽  
Pilot Studies ◽  
Cytoplasmic Staining ◽  
Time Interaction ◽  
Normal Keratinocytes ◽  
Keratinocyte Cell ◽  
Permeability Studies

Canine progenitor epidermal keratinocytes (CPEK) are used as canine keratinocyte cell line. Their suitability for skin barrier studies is unknown. Measurement of transepithelial electric resistance (TEER) evaluates epithelial permeability. We compared TEER and tight junction (TJ) expression in CPEKs and normal keratinocytes (NK) harvested from biopsies of normal dogs. CPEKs and NK were grown until confluence (D0) and for 13 additional days. Slides were fixed on D0 and stained with ZO-1 and claudin-1 antibodies. Five images/antibody were taken, randomized and evaluated blindly by three investigators for intensity, staining location, granularity, and continuousness. Cell size and variability were evaluated. TEER increased overtime to 2000 Ohms/cm in NK, while remained around 100–150 Ohms/cm in CPEK. ANOVA showed significant effect of time (p < 0.0001), group (p < 0.0001) and group x time interaction (p < 0.0001) for TEER. Size of CPEKs was significantly (p < 0.0001) smaller and less variable (p = 0.0078) than NK. Intensity of claudin-1 staining was greater in CPEKs (p < 0.0001) while granularity was less in CPEKs (p = 0.0012). For ZO-1, cytoplasmic staining was greater in CPEK (p < 0.0001) while membrane continuousness of staining was greater in NK (p = 0.0002). We conclude that CPEKs grown in monolayer are not representative of NK for permeability studies.

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