M Charveron's research while affiliated with Centre de Recherche Pierre Fabre and other places
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Publications (145)
Cell adhesion molecules, such as E-selectin or intercellular adhesion molecule 1 (ICAM-1), play an important role in mediating leucocyte capture and rolling on the surface of blood vessels in atopic skin. The effectiveness of Avène hydrotherapy in patients suffering from atopic dermatitis has previously been demonstrated. Thus, we examined the effe...
Peptidylarginine deiminases (PADs) catalyze deimination, converting arginyl to citrullyl residues. Only three PAD isotypes are detected in the epidermis where they play a crucial role, targeting filaggrin, a key actor for the tissue hydration and barrier functions. Their expression and activation depends on the keratinocyte differentiation state. T...
Previous studies have established that UV irradiation results in epidermal growth factor receptor (EGFR) activation in keratinocytes. However, the signaling pathways and cellular effects related to this process remain incompletely elucidated. Herein, we describe for the first time that UVA-mediated EGFR activation results in beta-catenin tyrosine p...
Gingival tissue faces constant exposure to micro-organisms. It functions as part of the host response, an anti-microbial barrier that recognizes and discriminates between commensal and pathogenic bacteria. This study aimed to evaluate and compare the effects of cell wall extracts from different periodontal bacteria, commensals Streptococcus sanguin...
The skin commensal bacillus Propionibacterium acnes is known to play a major role in the development of acne vulgaris and it is established that this bacteria is involved both in the induction and maintenance of the inflammatory phase of acne. The corticotropin releasing hormone (CRH), a neuropeptide originally isolated from the hypothalamus, is al...
The keratinocyte growth and differentiation switch, tightly regulated by several mechanisms, is generally associated with decreased proliferation, cell cycle arrest in G0/G1 phase and expression of epidermal differentiation markers, such as keratin 1 (K1), keratin 10 (K10) and involucrin. In vitro, the spontaneously immortalized human keratinocyte...
Long-range cis elements are critical regulators of transcription, particularly for clustered paralogous genes. Such are the five PADI genes in 1p35-36 encoding peptidylarginine deiminases, which catalyze deimination, a Ca2+-dependent post-translational modification. Deimination has been implicated in the pathophysiology of severe human diseases suc...
Oligonucleotide probes used in this study
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3C detailed protocol for NHEKs
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Recent reports revealed that neural mechanisms play a role in hair growth control. An induction of murine hair growth is obtained after treatment with substance P (SP). In this study, we examined the expression of a SP receptor: the neurokinin-1 (NK1-R) during: 1) the human hair cycle, 2) on isolated hair follicle, and 3) in cultured hair dermal pa...
During cutaneous inflammatory diseases, the neuro-immuno-cutaneous system is impaired. In atopic dermatitis pathology, a perturbation of neuromediators release such as substance P (SP), calcitonin gene-related peptide (CGRP) and bradykinin (BK) could be in part involved in the neurogenic inflammatory state; both of these peptides identified in huma...
Aberrant keratinocyte differentiation is considered to be a key mechanism in the onset of hyperproliferative dermatological diseases, including basal cell carcinoma (BCC). It is, therefore, vital to understand what drives keratinocytes to develop such pathological phenotypes. The role of calcium in keratinocyte differentiation is uncontested but th...
As shown by atopy patch tests, atopic dermatitis (AD) is dominated in its acute phase by the development of a specific T(H)2 response after exposure of the skin to common environmental antigens. Relying on our previous data showing that Staphylococcus aureus enterotoxin B (SEB) induced the activation of monocyte-derived dendritic cells (DCs) throug...
Cyclobutane pyrimidine dimers (CPDs) and pyrimidine (6-4) pyrimidone photoproducts (6-4PPs) are the two main classes of mutagenic DNA damages induced by UVB radiation. Numerous studies have been devoted so far to their formation and repair in human cells and skin. However, the biochemical methods used often lack the specificity that would allow the...
Transcription control at a distance is a critical mechanism, particularly for contiguous genes. The peptidylarginine deiminases (PADs) catalyse the conversion of protein-bound arginine into citrulline (deimination), a critical reaction in the pathophysiology of multiple sclerosis, Alzheimer's disease and rheumatoid arthritis, and in the metabolism...
Propionibacterium acnes plays an important role in the pathogenesis of acne and it is established that this bacteria is involved in the induction and maintenance of the inflammatory phase of acne. The aim of our work was to determine if P. acnes extracts could modulate integrins and filaggrin in vitro expression by keratinocytes. Integrins and fila...
UVA irradiation contributes largely to photocarcinogenesis. In the process of keratinocyte transformation, the activation of EGFR by UV is now considered as a critical event. However, the mechanism that links the EGFR pathway and photocarcinogenesis is not totally understood. In this study, we report that the EGFR/Akt pathway mitigated G2/M arrest...
Polyunsaturated fatty acids (PUFA) n-3 inhibit inflammation, in vivo and in vitro in keratinocytes. We examined in HaCaT keratinocyte cell line whether eicosapentaenoic acid (EPA) a n-3 PUFA, gamma-linoleic acid (GLA) a n-6 PUFA, and arachidic acid a saturated fatty acid, modulate expression of cyclooxygenase-2 (COX-2), an enzyme pivotal to skin in...
Gingival innate immunity has been studied by using biopsies and normal or transformed epithelial cell monolayers. To overcome individual biological variabilities and as a physiological alternative, we have proposed using a reconstructed tissue equivalent. In this study, we investigated the functionality and the stage of differentiation of a reconst...
In a previous study, we have described that UVB induces granzyme B (GrB) in human keratinocyte cells, and that confers potent
cellular cytotoxicity against various cellular models, including immune cells (Hernandez-Pigeon, H., Jean, C., Charruyer,
A., Haure, M. J., Titeux, M., Tonasso, L., Quillet-Mary, A., Baudouin, C., Charveron, M., and Laurent,...
During embryonic development, feathers appear first as primordia consisting of an epidermal placode associated with a dermal condensation. When 7-day chick embryo dorsal skin fragments showing three rows of feather primordia are cultured, they undergo a complete reorganization, which involves the down-regulation of morphogenetic genes and dispersal...
Propionibacterium acnes (P. acnes) plays an important role in the induction and maintenance of the inflammatory phase of acne. At the therapeutic level, it has been shown that zinc salts could have a beneficial effect on mild and moderate inflammatory acne lesions. However, their mechanisms of action are still only partially known. Immediate early...
Solar UV radiation is the most important environmental factor involved in the pathogenesis of skin cancers. The well known genotoxic properties of UVB radiation (290–320 nm) mostly involve bipyrimidine DNA photoproducts. In contrast, the contribution of more-abundant UVA radiation (320–400 nm) that are not directly absorbed by DNA remains poorly un...
We have designed experimental conditions allowing the replacement of 50% of cholesterol of human keratinocytes (SVK14 line) with sitosterol or stigmasterol without affecting cellular viability. We have investigated the influence of incorporating phytosterol on the ultraviolet-A-induced formation of lipid-peroxidation products (thiobarbituric reacti...
Immune surveillance against microbes at sites of interface with environment involves immediate recognition of pathogen-associated molecular patterns by dendritic cells (DCs). According to their first-line position, DCs are key parameters for the establishment of an appropriate innate and adaptive response against pathogens to avoid disease developm...
Ultraviolet (UV) radiation from the sun is widely considered as a major cause of human skin photoaging and skin cancer. Granzyme B (GrB) and perforin (PFN) are two proteins contained in granules and implicated in one of the mechanisms by which cytotoxic lymphocytes and natural killer cells exert their cytotoxicity against virus-infected, alloreacti...
Exposure of the skin to UVB light results in the formation of DNA photolesions that can give rise to cell death, mutations, and the onset of carcinogenic events. Specific proteins are activated by UVB and then trigger signal transduction pathways that lead to cellular responses. An alteration of these signaling molecules is thought to be a fundamen...
Deimination, a post-translational modification catalyzed by peptidylarginine deiminases (PADs), appears as a crucial Ca(2+)-dependent event in the last steps of epidermal differentiation. In normal human epidermis, where the deiminated proteins are filaggrin and keratins, PAD1, 2 and 3 are expressed but their relative role is unknown. The three PAD...
Peptidylarginine deiminases (PAD) catalyze the conversion of arginine residues to citrullines. Five isoforms are known that present distinct tissue locations. In the epidermis, like in the skin, only PAD1, 2, and 3 are expressed. Their pattern of expression in skin appendages is not known. Here, confocal microscopy analysis using highly specific an...
Induction of DNA damage by solar UV radiation is a key event in the development of skin cancers. Bipyrimidine photoproducts, including cyclobutane pyrimidine dimers (CPDs), (6-4) photoproducts (64 PPs) and their Dewar valence isomers, have been identified as major UV-induced DNA lesions. In order to identify the predominant and most persistent lesi...
The aim of the present study was to examine the effects of Avena Rhealba (AR) oatmeal extract on the metabolism of arachidonic acid (AA) and eicosanoids as well as on the expression of cytosolic phospholipase A(2 )(cPLA(2)) in the human keratinocyte cell line HaCaT. For this purpose, we examined the effects of AR on basal and A23187-triggered relea...
Post-translational conversion of arginine to citrulline residues is catalyzed by peptidylarginine deiminases (PAD). Although the existence of five isoforms of PAD has been reported in rodents and humans, their tissue distribution, substrate specificity, and physiological function have yet to be explored. In the epidermis, deimination of filaggrin a...
Exposure to solar ultraviolet light is the major cause of most skin cancers. While the genotoxic properties of UVB radiation are now well understood, the DNA damaging processes triggered by less energetic but more abundant UVA photons remain to be elucidated. Evidence has been provided for the induction of oxidative lesions to cellular DNA includin...
DNA repair plays a central role in the cellular response to UV. In this work we have studied the response of skin cells (i.e. fibroblasts and keratinocytes) from the same or from different individuals after both ultraviolet-B (UV-B) and ultraviolet-C (UV-C) irradiations using the comet assay to characterize the specific cellular response to UV-indu...
Mutagenic and carcinogenic UV-B radiation is known to damage DNA mostly through the formation of bipyrimidine photoproducts, including cyclobutane dimers (CPD) and (6-4) photoproducts ((6-4) PP). Using high-performance liquid chromatography coupled to tandem mass spectrometry, we investigated the formation and repair of thymine-thymine (TT) and thy...
Phospholipases A2 (PLA2) are enzymes that catalyse the hydrolysis of glycerophospholipids at the sn-2 position, generating free fatty acids and lysophospholipids. At present, PLA2 family consists of 12 groups. PLA2 are involved in many pathophysiological processes such as barrier function, eicosanoid production, and inflammation. They are implicate...
Phospholipases A2 (PLA2) are enzymes that catalyse the hydrolysis of glycerophospholipids at the sn-2 position, generating free fatty acids and lysophospholipids. At present, PLA2 family consists of 12 groups. PLA2 are involved in many pathophysiological processes such as barrier function, eicosanoid production, and inflammation. They are implicate...
Phospholipase B (PLB) is an enzyme that displays both phospholipase A(2) and lysophospholipase activities. Analysis of human epidermis homogenates indicated the presence of a 97 kDa PLB protein, as well as a phospholipase A(2) activity, both being enriched in the soluble fraction. Immunolabelling and in situ hybridization experiments showed that th...
Human hair follicles progress independently through the anagen, catagen, telogen and latency phases that correspond to growth arrest and hair shedding before initiation of a new anagen phase. Hair follicles are self-renewing and contain reservoirs of multi-potent stem cells. Identification of the messenger molecules and pathways operating in the gr...
We are increasingly exposed to environmental pollution. Pollutants can be inhaled, ingested or come into contact with the skin depending on the form in which they occur. On metabolization, activation, or accumulation, pollutants can become extremely toxic for the vital organs and this is often related to a strong genotoxic effect. Since the skin ac...
F 11782, or 2'', 3''-bispentafluorophenoxyacetyl-4, 6'-ethylidene-beta-D glucoside of 4'-phosphate-4'-dimethylepipodopliyllotoxin 2N-methyl glucamine salt, is a novel fluorinated lipophylic epipodophylloid which has shown marked antitumour activity in vivo. In vitro studies have demonstrated a dual catalytic inhibitory activity of F 11782 against t...
Avène spring water (ASW) is commonly used in France for treating atopic dermatitis and psoriasis. Previous works demonstrated modulation of cell membrane fluidity by ASW. The aims of the present study were (a) to investigate a possible in vitro effect of ASW on Th1- and Th2-dependent cytokine production using peripheral blood mononuclear cells from...
Phospholipases A2 are enzymes that catalyze the release of fatty acids from the sn-2 position of phospholipids. Fatty acids have been suggested to play a key role in the barrier function of the epidermis. The aim of this study was to identify and characterize the type of secretory phospholipase A2 expressed in human epidermis. We report the molecul...
Phospholipases A2 (PLA2) catalyse the release of fatty acids from the sn-2 position of phospholipids and have been suggested to play a key part in permeability barrier homeostasis. Using a sensitive and versatile fluorometric method, significant PLA2 activity has been detected in both human skin homogenates and tape strippings of stratum corneum. B...
Cutaneous parameters such as dermal thickness, stiffness, elasticity, skin surface lipid and hydration were evaluated using noninvasive methods in 77 growth hormone-deficient (GHD) children before replacement therapy and in 70 non-GHD children. We showed that in GHD children, dermis was thinner (0.70 +/- 0.10 vs. 0.80 +/- 0.10 mm, p < 0.0001 for pr...
The known role of steroids on the hair follicle leads us to investigate their effects on hair follicle cell angiogenic responses in vitro. We verified, using the immunohistochemical technique, whether human occipital scalp follicle cells express steroid receptors in vitro. We showed that androgen and estrogen receptors were expressed by dermal papi...
The in vitro effects of plant sterols were investigated with regard to their uptake and membrane lipid fluidity in human keratinocytes. Among the different media tested to transport sterols (liposomes, micelles and organic solvents), the best results in terms of incorporation and viability were obtained by the use of the organic solvents dimethylsu...
An 18-year old boy with dyskeratosis congenita is presented. To examine the DNA metabolism of our patient, we applied the comet assay, a simple, quick and sensitive method that so far has not been used in this disease. After exposure to UVB, cells originating from the patient present abnormal DNA repair localized in the late step. We consider that...