Home About us Contact
|
Home About us Contact | ||
|
|
||
Keratinocyte Proliferation (keratinocyte + proliferation)
Selected AbstractsHypotonic stress influence the membrane potential and alter the proliferation of keratinocytes in vitroEXPERIMENTAL DERMATOLOGY, Issue 4 2007Mónika Gönczi Abstract:, Keratinocyte proliferation and differentiation is strongly influenced by mechanical forces. We investigated the effect of osmotic changes in the development of HaCaT cells in culture using intracellular calcium measurements, electrophysiological recordings and molecular biology techniques. The application of hypotonic stress (174 mOsmol/l) caused a sustained hyperpolarization of HaCaT cells from a resting potential of ,27 ± 4 to ,51 ± 9 mV. This change was partially reversible. The surface membrane channels involved in the hyperpolarization were identified as chloride channels due to the lack of response in the absence of the anion. Cells responded with an elevation of intracellular calcium concentration to hypotonic stress, which critically depended on external calcium. The presence of phorbol-12-myristate-13-acetate in the culture medium for 12 h augmented the subsequent response to hypotonic stress. A sudden switch from iso- to hypotonic solution increased cell proliferation and suppressed the production of involucrin, filaggrin and transglutaminase, markers of keratinocyte differentiation. It is concluded that sudden mechanical forces increase the proliferation of keratinocytes through alterations in their membrane potential and intracellular calcium concentration. These changes together with additional modifications in channel expression and intracellular signalling mechanisms could underlie the increased proliferation of keratinocytes in hyperproliferative skin diseases. [source] Gastrin-Releasing Peptide, a Bombesin-like Neuropeptide, Promotes Cutaneous Wound HealingDERMATOLOGIC SURGERY, Issue 4 2002Yuji Yamaguchi MD Background. Little is known about the effects of neuropeptides on wound healing. Objective. To investigate the effect of gastrin-releasing peptide (GRP), one of the bombesin-like neuropeptides, on wound healing. Methods. The effects of GRP on cultured keratinocyte proliferation and migration were measured by BrdU uptake and in vitro scratch assay, respectively. Various concentrations of GRP ointments (0, 10,9, 10,8, 10,7, 10,6 M) were topically applied to 1.0 mm wounds on porcine flanks. Results. GRP stimulated keratinocyte growth and locomotion in a dose-dependent manner. Topical administration of GRP accelerated macroscopic epidermal regeneration in a dose-dependent manner, as measured by planimetry. Histologic studies also showed that GRP promoted reepithelialization, including epidermal thickness as well as superficial skin coverage. conclusion. Topical use of GRP may clinically accelerate wound healing of burns, injuries, chronic ulcers, and skin graft donor sites through the enhancement of keratinocyte growth and spreading. [source] The role of the cutaneous cholinergic system in guttate psoriasisEXPERIMENTAL DERMATOLOGY, Issue 7 2008W. Dyck In previous studies, high levels of acetylcholine (ACh) have been reported in psoriasis lesions. In addition, patients with guttate psoriasis respond to oral treatment with atropine. We wanted to know how the cutaneous cholinergic system could be involved in this process. Since mast cells (MC) are characteristic components of the inflammatory infiltrate of guttate psoriasis, we compared ACh receptor (AChR) composition and ACh production in both epidermis and mast cells of 10 patients with guttate psoriasis in involved and uninvolved skin on protein level using immunofluorescence and in a MC line (HMC-1) using PCR. We could confirm the presence of numerous MC in guttate psoriasis lesion. Both in vivo and in vitro, MC lacked expression of cholinacetyltransferase (ChAT), vesicular acetylcholintransorter (VAChT) and cholintransporter-1 (ChT-1) but contained high levels of acetylcholinesterase (AChE). In mast cells of both involved and uninvolved skin we found both nicotinic (,3, ,5, ,7, ,9, ,10, ,2 and ,4 subunits) and muscarinic (M1, M3, M4, M5) AChR. In HMC-1 cells all AChR subunits found in skin where present on mRNA level, except ,7 and ,2. In lesional epidermis both ACh production and AChR expression was shifted from the basal to the suprabasal layers especially the nicotinic ,3, ,5, ,9, ,2 and ,4 and the muscarinic M3 and M5 AChR subunits. Our results exclude a role of the cholinergic system in the initiation of keratinocyte proliferation in the basal epidermal layer but point towards a role of epidermal AChR in suprabasal processes, most likely terminal differentiation and barrier formation as has been shown in other systems. Most importantly, mast cells are targets of paracrine and endocrine effects mediated by ACh and choline thus modulating inflammatory processes like guttate psoriasis and explaining the clinical efficacity of anticholinergic drugs like atropine. [source] Terrein inhibits keratinocyte proliferation via ERK inactivation and G2/Mcell cycle arrestEXPERIMENTAL DERMATOLOGY, Issue 4 2008Dong-Seok Kim Abstract:, Terrein, a fungal metabolite, has been recently shown to have a strong antiproliferative effect on skin equivalents. In the present study, we further investigated the effects of terrein on the possible signalling pathways involved in the growth inhibition of human epidermal keratinocytes by examining the regulations of extracellular signal-regulated protein kinase (ERK) and of the Akt pathway by terrein. It was observed that ERK was inactivated by terrein and that keratinocyte proliferation was inhibited, whereas Akt was unaffected. The inhibition of the ERK pathway by U0126 (a specific ERK inhibitor) also had a dose-dependent antiproliferative effect on human keratinocytes. These results indicate that ERK inhibition is involved in keratinocyte growth inhibition by terrein. Moreover, flow cytometric analysis showed that terrein inhibits DNA synthesis, as evidenced by a reduction in the S phase and an increase in the G2/M phase of the cell cycle. Thus, we next examined changes in the expressions of G2/M cell cycle-related proteins. Terrein was found to downregulate cyclin B1 and Cdc2 without Cdc2 phosphorylation, but upregulated p27KIP1 (p27), a known inhibitor of cyclin-dependent kinase. These results suggest that terrein reduces human keratinocyte proliferation by inhibiting ERK and by decreasing the expressions of cyclin B1 and Cdc2 complex. [source] Topical treatment with thiazolidinediones, activators of peroxisome proliferator-activated receptor-,, normalizes epidermal homeostasis in a murine hyperproliferative disease modelEXPERIMENTAL DERMATOLOGY, Issue 3 2006Marianne Demerjian Abstract:, In a murine model of epidermal hyperplasia reproducing some of the abnormalities of several common skin disorders, we previously demonstrated the antiproliferative and pro-differentiating effects of peroxisome proliferator-activated receptor (PPAR),, PPAR,/,, and liver X receptor activators. Unlike other subgroups of PPAR activators, thiazolidinediones (TZDs), a family of PPAR, ligands, did not inhibit keratinocyte proliferation in normal murine skin. Here, we studied the effects of two TZDs, namely ciglitazone (10 mM) and troglitazone (1 mM), in the same murine model where epidermal hyperproliferation was reproduced by repeated barrier abrogation with tape stripping. Topical treatment with ciglitazone and troglitazone resulted in a marked and significant decrease in epidermal thickness. Furthermore, in all TZD-treated groups, we observed a significant decrease in keratinocyte proliferation using proliferating cell nuclear antigen, 5-bromo-2,-deoxyuridine, and tritiated thymidine incorporation. However, using the terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling assay, we found no difference in apoptosis between different treatments, emphasizing that it is the antiproliferative role of these activators that accounts for the decrease of epidermal thickness. Finally, using immunohistochemical methods, we determined the effects of ciglitazone on keratinocyte differentiation in this hyperproliferative model. We observed an increased expression of involucrin and filaggrin following ciglitazone treatment, suggesting a pro-differentiating action of TZDs in this model. In summary, topical TZDs significantly reduce epidermal keratinocyte proliferation while promoting differentiation in a murine model of hyperproliferative epidermis. Together, these results suggest that in addition to their metabolic effects currently in use in the treatment of type 2 diabetes, topical TZDs could be considered as potential alternative therapeutic agents in hyperproliferative skin diseases such as psoriasis. [source] In vitro induction of matrix metalloproteinase-2 and matrix metalloproteinase-9 expression in keratinocytes by boron and manganeseEXPERIMENTAL DERMATOLOGY, Issue 8 2004Nathalie Chebassier Abstract:, Matrix metalloproteinase (MMP)-2 and MMP-9 are involved in keratinocyte migration and granulation tissue remodeling during wound healing. Thermal water cures are sometimes proposed as complementary treatment for accelerating healing of wounds resulting from burns and/or surgery, but their mechanisms of action remain unknown. Some thermal waters are rich in trace elements such as boron and manganese. Interestingly, clinical studies have shown the beneficial effects of trace elements such as boron and manganese for human wound healing. To try to specify the role of trace elements in cutaneous healing, the present study investigated the effects of these trace elements on the production of MMP-2 and MMP-9 by normal human keratinocytes cultured in vitro. Immunohistochemistry and Western blot showed that intracellular MMP-9 expression in keratinocytes was induced when incubated for 6 h with boron at 10 µg/ml or manganese at 0.2 µg/ml. Moreover, gelatin zymography on keratinocyte supernatants showed an increase of gelatinase secretion after 24 h of incubation of keratinocytes with boron or manganese, regardless of concentration. Gelatinase secretion was not associated with keratinocyte proliferation induced by trace elements. Thus, our results suggest that boron and manganese could play a role in the clinical efficiency of thermal water on wound healing. [source] Possible involvement of epidermodysplasia verruciformis human papillomaviruses in the immunopathogenesis of psoriasis: a proposed hypothesisEXPERIMENTAL DERMATOLOGY, Issue 6 2003Slawomir Majewski Abstract:, We have shown previously in psoriasis a very high prevalence of epidermodysplasia verruciformis-associated human papillomavirus 5 (EVHPV5) DNA and antibodies to human papillomavirus 5 (HPV5) virus-like particle (VLP)L1, and we suggested that this benign hyperproliferative disorder could be a reservoir for EVHPVs. Here we provide new data confirming the expression of EVHPVs in psoriasis and present our hypothesis on their possible involvement in the immunopathogenesis of the disorder. The new important finding was detection by a radioimmunoprecipitation assay of a very high prevalence of antibodies to E6/E7 HPV5 oncoproteins, known to enhance keratinocyte proliferation. More recently, EV genes were identified, EVER1 and EVER2, whose mutations are responsible for epidermodysplasia verruciformis. Epidermodysplasia verruciformis-associated human papillomaviruses are harmless to the general population as a result of genetic restriction, which in psoriasis appears to be partly alleviated, and this may allow the viral gene expression. We hypothesize that induction of keratinocyte proliferation in psoriasis by various stimuli initiates the EVHPV life cycle with expression of early (E6/E7) and late (L1) viral proteins. The early proteins may, in turn, enhance the keratinocyte proliferation, and the late proteins could serve as a target for specific B- and T-cell-mediated responses. Immune responses against the viral antigens in the epidermis may result in chemoattraction of leukocytes and Munro abscess formation, as well as in production of proinflammatory cytokines, leading to self perpetuation of the psoriatic process. The novel immunomodulatory therapies could also inhibit immune responses against EVHPV proteins, leading to decreased cytokine production, keratinocyte proliferation and EVHPV expression. Thus the beneficial effect of these therapies is not discordant with the proposed hypothesis of possible involvement of EVHPVs in the immunopathogenesis of psoriasis. [source] Nickel-induced keratinocyte proliferation and up-modulation of the keratinocyte growth factor receptor expressionEXPERIMENTAL DERMATOLOGY, Issue 4 2003Cinzia Marchese Abstract: Keratinocytes play a key role in the pathogenesis of allergic contact dermatitis (ADC) induced by the sensitizing agent nickel. We analyzed here the effects of treatment with nickel and of the pretreatment with zinc on HaCaT cells and primary human keratinocytes. Cell counting, 5-bromo-2,-deoxyuridine incorporation assay and adenosine triphosphate (ATP) bioluminescence detection showed that treatment with NiSO4 induced DNA synthesis and cell proliferation and that pretreatment with ZnSO4 was able to abrogate this proliferative effect. This nickel-induced cell growth appeared enhanced when primary human keratinocytes were co-cultured with fibroblasts. Western blot analysis demonstrated that nickel ions induced up-modulation of the expression of the keratinocyte growth factor receptors (KGFR) without affecting the keratinocyte differentiation, whereas the protein levels of the epidermal growth factor receptor (EGFR) and of its ligand transforming growth factor-alpha (TGF-,) appeared unmodified by the treatment. Double immunofluorescence showed that the effect of nickel on DNA synthesis was mainly exerted on KGFR expressing cells, suggesting that KGFR up-modulation could be required for the nickel-induced cell proliferation. These results indicate that KGFR and its ligands may play a role in the mechanism of action of nickel ions and in the protective effect of zinc pretreatment. [source] Zinc, copper and manganese enhanced keratinocyte migration through a functional modulation of keratinocyte integrinsEXPERIMENTAL DERMATOLOGY, Issue 6 2000I. Tenaud Abstract: The migration of keratinocytes plays an important role in the re-epithelialization of cutaneous wounds. Zinc, copper and manganese are used in vivo for their healing properties and their mechanism of action is still only partially known. Thus, they have been shown both to promote keratinocyte proliferation and to modulate integrins expression. The aim of this study was to determine if trace elements induce an increase of the migration of keratinocytes and if this effect is related to the modulation of integrins. Two independent migration assays were used to study keratinocyte migration: the scratch assay using normal human keratinocytes and the modified Boyden chamber using HaCaT cells. Inhibition studies using function-blocking antibodies directed to ,3, ,6, ,V and ,1 subunits were performed to investigate the modulator effect of trace elements on integrin function. In this way, zinc and copper gluconates increased ,3, ,V and ,1 function whereas manganese gluconate seems mainly able to modulate the function of ,3 and ,1. The stimulating effect of these trace elements on keratinocyte migration does not appear related to ,6 subunit. Thus, zinc, copper and manganese enhanced keratinocyte migration and one of the mechanisms was going through a modulation of integrin functions. [source] Two modes of ERK activation by TNF in keratinocytes: Different cellular outcomes and bi-directional modulation by vitamin D,JOURNAL OF CELLULAR BIOCHEMISTRY, Issue 2 2008Ester Ziv Abstract Inflammation, elicited in the skin following tissue damage or pathogen invasion, may become chronic with deleterious consequences. Tumor necrosis factor (TNF) is a key mediator of cutaneous inflammation and the keratinocyte an important protagonist of skin immunity. Calcitriol, the hormonally active vitamin D metabolite, and its analogs attenuate epidermal inflammation and inhibit the hyperproliferation of keratinocytes associated with the inflammatory disorder, psoriasis. Since activation of extracellular signal-regulated kinase (ERK) promotes keratinocyte proliferation and mediates epidermal inflammation, we studied the effect of calcitriol on ERK activation in HaCaT keratinocytes exposed to the ubiquitous inflammatory cytokine TNF. By using the EGF receptor (EGFR) tyrosine kinase inhibitor, AG1487 and the Src family inhibitor, PP-1, we established that TNF activated ERK in an EGFR and Src dependent and an EGFR and Src independent modes. EGFR dependent activation resulted in the upregulation of the transcription factor, c-Fos, while the EGFR independent activation mode was of a shorter duration, did not affect c-Fos expression but induced IL-8 mRNA expression. Pretreatment with calcitriol, enhanced TNF-induced EGFR-Src dependent ERK activation and tyrosine phosphorylation of the EGFR, but abolished the EGFR-Src independent ERK activation. These effects were mirrored by enhancement of c-Fos and inhibition of IL-8 induction by TNF. Treatment with calcitriol increased the rate of the de-phosphorylation of activated ERK, accounting for the inhibition of EGFR-Src independent ERK activation by TNF. It is possible that effects on the ERK cascade contribute to the effects of calcitriol and its synthetic analogs on cutaneous inflammation and keratinocyte proliferation. J. Cell. Biochem. 104: 606,619, 2008. © 2007 Wiley-Liss, Inc. [source] Decreased Srcasm expression in hyperproliferative cutaneous lesionsJOURNAL OF CUTANEOUS PATHOLOGY, Issue 3 2009Marc C. Meulener Background:, Src-family tyrosine kinases (SFKs) are signaling proteins that regulate keratinocyte proliferation and differentiation. Src-activating and signaling molecule (Srcasm) is a recently identified molecule that downregulates SFK activity and promotes keratinocyte differentiation. To determine if Srcasm expression correlates with keratinocyte differentiation, we characterized the level of Srcasm expression in some cutaneous lesions that exhibit increased keratinocyte proliferation. Methods:, Formalin-fixed sections of randomly selected seborrheic keratoses (SKs) and basal cell carcinomas (BCCs) were analyzed for Srcasm and Ki-67 immunohistochemical staining. Anti-Srcasm and anti-Ki-67 stainings were performed in parallel. Results:, All SKs displayed decreased Srcasm staining in areas comprised of basaloid keratinocytes that exhibited an increased Ki-67 index. Higher Srcasm staining levels were detected near pseudohorn cysts where keratinocytes exhibited a lower Ki-67 index. All multicentric and nodular BCCs displayed a prominent loss of Srcasm staining in association with a marked increase in Ki-67 staining. Conclusions:, Our results support the hypothesis that Srcasm protein levels are decreased in the hyperproliferative keratinocytes found in SKs and BCCs. Increased Srcasm protein levels are detected in keratinocytes undergoing differentiation. Decreased Srcasm levels may be part of the pathophysiologic mechanism in cutaneous lesions, exhibiting keratinocyte hyperproliferation. [source] Review of Pododermatitis Circumscripta (Ulceration of the Sole) in Dairy CowsJOURNAL OF VETERINARY INTERNAL MEDICINE, Issue 4 2006Sarel R. van Amstel Sole ulcers are among the most frequent causes of lameness in dairy cattle. They are found most commonly in the hind lateral claw, are frequently bilateral, and have a high rate of reoccurrence. The pathogenesis of sole ulceration is primarily based on mechanical injury by the 3rd phalanx to the corium, basement membrane, and basal layers of the sole epidermis as a result of failure of the suspensory apparatus in the claw. The main pathways in the failure of the suspensory system include inflammatory (dermal vascular changes followed by disruption of keratinocyte proliferation and differentiation caused by local and systemic mediators) and noninflammatory (hormonal and biochemical changes in the peripartum period resulting in alterations of connective tissue in the suspensory system) pathways. Sole ulcers tend to occur in specific locations; the most reported site is the junction of the axial heel and sole. Other locations include the apex of the toe and the heel. Varying degrees of lameness may result, and the most severe are seen with complicated cases in which ascending infection affects the deeper structures of the claw. Pathologic changes at the ulcer site include dyskeratosis and dilated horn tubules with microcracks. Vascular changes include dilatation and thrombosis of capillaries with "neocapillary formation." Areas of dyskeratosis may remain for as long as 50 days at the ulcer site. Treatment includes corrective trimming and relief of weight bearing. Complicated cases may require surgical intervention. [source] Requirement for Metalloproteinase-dependent ERK and AKT Activation in UVB-induced G1-S Cell Cycle Progression of Human KeratinocytesPHOTOCHEMISTRY & PHOTOBIOLOGY, Issue 4 2009Weinong Han UVB (280,315 nm) in natural sunlight represents a major environmental challenge to the skin and is clearly associated with human skin cancer. Here we demonstrate that low doses of UVB induce keratinocyte proliferation and cell cycle progression of human HaCaT keratinocytes. Different from UVA, UVB irradiation induced extracellular signal-regulated kinase (ERK) and AKT activation and their activation are both required for UVB-induced cell cycle progression. Activation of epidermal growth factor receptor (EGFR) was observed after UVB exposure and is upstream of ERK/AKT/cyclin D1 pathway activation and cell cycle progression following UVB radiation. Furthermore, metalloproteinase (MP) inhibitor GM6001 blocked UVB-induced ERK and AKT activation, cell cycle progression, and decreased the EGFR phosphorylation, demonstrating that MPs mediate the EGFR/ERK/AKT/cyclin D1 pathways and cell cycle progression induced by UVB radiation. In addition, ERK or AKT activation is essential for EGFR activation because ERK or AKT inhibitor blocks EGFR activation following UVB radiation, indicating that EGFR/AKT/ERK pathways form a regulatory loop and converge into cell cycle progression following UVB radiation. Identification of these signaling pathways in UVB-induced cell cycle progression of quiescent keratinocytes as a process mimicking tumor promotion in vivo will facilitate the development of efficient and safe chemopreventive and therapeutic strategies for skin cancer. [source] Human lactoferrin stimulates skin keratinocyte function and wound re-epithelializationBRITISH JOURNAL OF DERMATOLOGY, Issue 1 2010L. Tang Summary Background, Human lactoferrin (hLF), a member of the transferrin family, is known for its antimicrobial and anti-inflammatory effects. Recent studies on various nonskin cell lines indicate that hLF may have a stimulatory effect on cell proliferation. Objectives, To study the potential role of hLF in wound re-epithelialization. Materials and methods, The effects of hLF on cell growth, migration, attachment and survival were assessed, with a rice-derived recombinant hLF (holo-rhLF), using proliferation analysis, scratch migration assay, calcein-AM/propidium iodide staining and terminal deoxynucleotidyl transferase-mediated dUTP nick-end labelling (TUNEL) method, respectively. The mechanisms of hLF on cell proliferation and migration were explored using specific pathway inhibitors. The involvement of lactoferrin receptor low-density lipoprotein receptor-related protein 1 (LRP1) was examined with RNA interference technique. An in vivo swine second-degree burn wound model was also used to assess wound re-epithelialization. Results, Studies revealed that holo-rhLF significantly stimulated keratinocyte proliferation which could be blocked by mitogen-activated protein kinase (MAPK) kinase 1 inhibitor. Holo-rhLF also showed strong promoting effects on keratinocyte migration, which could be blocked by either inhibition of the MAPK, Src and Rho/ROCK pathways, or downregulation of the LRP1 receptor. With cells under starving or 12- O -tetradecanoylphorbol-13-acetate exposure, the addition of holo-rhLF was found greatly to increase cell viability and inhibit cell apoptosis. Additionally, holo-rhLF significantly increased the rate of wound re-epithelialization in swine second-degree burn wounds. Conclusions, Our studies demonstrate the direct effects of holo-rhLF on wound re-epithelialization including the enhancement of keratinocyte proliferation and migration as well as the protection of cells from apoptosis. The data strongly indicate its potential therapeutic applications in wound healing. [source] A new endogenous retroviral sequence is expressed in skin of patients with psoriasisBRITISH JOURNAL OF DERMATOLOGY, Issue 1 2005J-P. Molčs Summary Background, The origin of psoriasis, a chronic inflammatory skin disease involving keratinocyte proliferation, immune disturbances and complex inheritance, remains unknown. Human endogenous retroviruses (HERVs) are part of the normal human genome and their participation in the pathogenesis of various human diseases with complex genetic traits has been proposed. A possible role of HERVs in the induction of psoriasis was suggested many years ago. However, to date no study has searched for HERV expression in psoriasis. Objectives, To determine firstly, which HERV families are expressed in the psoriatic lesion and secondly, whether specific variants can be detected. Methods, HERV expression was analysed at the mRNA level after degenerated reverse transcription,polymerase chain reaction (RT,PCR) of retroviral pol sequences followed by sequencing. Screening for a specific variant was performed by RT,PCR on lesional and nonlesional psoriatic skin and compared with normal and atopic dermatitis skin. Results, We report the expression of three HERV families in psoriatic lesions, namely HERV-W, K and E. We then partially characterized a new endogenous retroviral variant, which was related to the ERV-9/HERV-W family. This sequence contains at least two open reading frames that could encode for a gag protein and a retroviral protease. The expression of this sequence was detected in 29 of 43 lesional psoriasis skin samples and rarely in normal (two of 21) or atopic dermatitis (three of 14) skin samples. Conclusions, In psoriatic lesions, HERV sequences of the W, K and E families are expressed and a new variant of the ERV-9/HERV-W family has been characterized. The possible role of HERV-related sequences in the pathogenesis of psoriasis is under investigation. [source] Ultraviolet B induces hyperproliferation and modification of epidermal differentiation in normal human skin grafted on to nude miceBRITISH JOURNAL OF DERMATOLOGY, Issue 4 2004S. Del Bino Summary Background For ethical and technical reasons, the in vivo biological effects of ultraviolet (UV) radiation on skin are difficult to study in human volunteers. The use of human skin grafted on to nude mice may circumvent this difficulty. Objectives To investigate the effects of a single moderate UVB exposure on human skin grafted on to nude mice. Methods Modifications of epidermal differentiation markers and patterns of keratin expression were assessed from 24 h to 14 days after a physiological UVB irradiation characterized by the induction of sunburn cells. Results During the first 48 h postexposure, involucrin, loricrin, transglutaminase type I, filaggrin and keratin K2e expression were altered together with the formation of abnormal horny layers. Constitutive keratin K14 was increased while keratin K10 expression was delayed. Newly synthesized keratins K6, K16, K17 and K19 were induced in parallel with an increase in the epidermal proliferation rate. A progressive normalization of both keratinocyte proliferation and differentiation took place during the following days, reaching completion within 2 weeks. Conclusions Exposure of human skin to a UVB dose corresponding to a mild sunburn reaction induces epidermal hyperproliferation and alterations of several constitutive differentiation markers, as well as a drastic modification in the pattern of epidermal keratins. Although these modifications were shown to be progressively reversed in a single exposure model, the data also suggest that subsequent UV exposures occurring during the recovery period may lead to potentially deleterious long-term consequences, such as photoageing and photocarcinogenesis. Grafted human skin appeared to be an attractive and promising model for investigating the biological consequences of UVB radiation in vivo. [source] Peroxisome proliferator-activated receptors in cutaneous biologyBRITISH JOURNAL OF DERMATOLOGY, Issue 2 2003S. Kuenzli Summary Peroxisome proliferator-activated receptors (PPARs) are ligand-activated transcription factors that regulate the expression of target genes involved in many cellular functions including cell proliferation, differentiation and immune/inflammation response. The PPAR subfamily consists of three isotypes: PPAR,, PPAR,/, and PPAR,, which have all been identified in keratinocytes. PPAR,/, is the predominant subtype in human keratinocytes, whereas PPAR, and PPAR, are expressed at much lower levels and increase significantly upon keratinocyte differentiation. PPAR,/, is not linked to differentiation, but is significantly upregulated upon various conditions that result in keratinocyte proliferation, and during skin wound healing. In vitro and in vivo evidence suggests that PPARs appear to play an important role in skin barrier permeability, inhibiting epidermal cell growth, promoting epidermal terminal differentiation and regulating skin inflammatory response by diverse mechanisms. These proprieties are pointing in the direction of PPARs being key regulators of skin conditions characterized by hyperproliferation, inflammatory infiltrates and aberrant differentiation such as psoriasis, but may also have clinical implications in inflammatory skin disease (e.g. atopic dermatitis), proliferative skin disease, wound healing, acne and protease inhibitor associated lipodystrophia. [source] Effects of moisturization on epidermal homeostasis and differentiationCLINICAL & EXPERIMENTAL DERMATOLOGY, Issue 1 2007R. W. Short Summary Moisturizers are commonly used for routine skin care. This study assessed the effects of a moisturizer on barrier function, epidermal architecture, keratinocyte proliferation, and physiological regulation of the epidermis in photoaged but otherwise normal skin. Fifteen women with moderately photoaged forearms were treated twice a day for 4 weeks with a moisturizer containing dimethicone and glycerine. Baseline and post-treatment transepidermal water loss (TEWL) and ipsilateral forearm biopsies were obtained. Epidermal thickness, melanin levels, keratinocyte proliferation, and expression of keratins were evaluated. Induction of keratins 6 and 16, commonly associated with keratinocyte proliferation and wound healing, was observed. Epidermal thickness increased by 0.019 mm (P = 0.005), barrier function improved (TEWL decreased by 13%) and melanin intensity decreased (P = 0.004). Even nonxerotic, photoaged skin may appear younger, benefiting structurally and functionally from routine use of moisturizers containing dimethicone and glycerine. [source] Transfection and ligation of CD40 in human oral keratinocytes affect proliferation, adhesion and migration but not apoptosis in vitroCLINICAL & EXPERIMENTAL DERMATOLOGY, Issue 2 2006M. Villarroel Dorrego Summary Aims:, CD40 expression is restricted to Keratinocytes of normal epidermis or stratified squamous epithelium of oral mucosa. Ligation of CD40 inhibits keratinocyte proliferation and apoptosis. The aim of this study was to investigate the functional significance of CD40 in the proliferation, apoptosis, adhesion and migration of human oral keratinocytes in vitro. Methods., The CD40-negative oral keratinocyte line OSC19, its CD40-positive transfected derivative (OSC19T-CD40) and null transfectants (OSC19T-control), with and without stimulation by soluble protein CD40 ligand (sCD40L) or anti-CD40 antibodies were used. Results., OSC19T-CD40 showed significantly (P < 0.001) slower growth than the null transfectants and parent cells. OSC19T-CD40 proliferation was inhibited by ligation with sCD40L and blocking by two anti-CD40 antibodies, but stimulated by a third. Binding of CD40 with ligand or antibody had no effect on keratinocyte apoptosis in any cell line. The capacity of OSC19T-CD40 cells to adhere to CD40L-coated wells was significantly greater (P < 0.001) than that of parent OSC19 and OSC19T-control cells, and the migration rate of OSC19T-CD40 cells was significantly higher than parent OSC19 (P = 0.038 on fibronectin, P = 0.004 on Matrigel) or OSC19T-control (P =0.017 on fibronectin, P = 0.013 on Matrigel) cells. Conclusions., CD40 is an important molecule in keratinocyte homeostasis, and has more than one ligand. The ligand that is bound may be critical in oral epithelial homeostasis, the development of malignancy and the behaviour of the subsequent tumour. [source] | |||||||||||||