Pruritus is one of the most common skin complaints, not always with a skin disease associated. Pruritus could hit every age group but its prevalence is high in elderly patients. Itch constitutive of pruritus can trigger sensitisation by histaminergic and non-histaminergic pathways. H1/H4 Histamine receptors stimulation, the histaminergic classical pathway will not be addressed in this study. Indeed, epidermal PAR-2 receptors (Protease-activated receptor-2) activation mediates cutaneous itch directly, not suppressed by antihistamine compound with a specific neuronal stimulation pathway (Davidson et al., 2010). TRPV1 channel (Transient receptor potential vanilloid 1) can be activated at the skin level by heat, pH and osmolarity modulation, physicochemical effects present during itch. Furthermore, its expression is increased in elderly patients epidermis (Lee YM et al., 2008). The aim of this work is to evaluate active ingredients to target PAR-2 and TRPV1 activation pathways to inhibit pruritus induction. The use of keratinocytes cell line HaCat allowed us to assess PAR-2 activity after stimulation by trypsin or SLIGKV-NH2 peptide agonist in monitoring Ca2+ flux signals. In this model, Polidocanol showed a significant dose response inhibitory activity after trypsin stimulation and a competitive activity against peptide agonist at the highest concentration. Prucidine-4® efficacy was tested on TRPV1 recombinant CHO cell based assay. Ca2+ flux signals modulation was measured after capsaïcin agonist stimulation. Prucidine-4® showed a significant dose response inhibition with a full reverse effect. These data suggest that a topical Dermo-Cosmetic product combining Polydocanol and Prucidine-4® compounds for their PAR-2 and TRPV1 inhibitory effects respectively could be useful to protect against pruritus induction.

Within their first days of life, newborns’ skin undergoes various adaptation processes needed to accommodate the transition from the wet uterine environment to the dry atmosphere. The skin of newborns and infants is considered as a physiological fragile skin, a skin with lower resistance to aggressions. Fragile skin is divided into four categories up to its origin: physiological fragile skin (age, location), pathological fragile skin (acute and chronic), circumstantial fragile skin (due to environmental extrinsic factors or intrinsic factors such as stress) and iatrogenic fragile skin. Extensive research of the past 10 years have proven evidence that at birth albeit showing a nearly perfect appearance, newborn skin is structurally and functionally immature compared to adult skin undergoing a physiological maturation process after birth at least throughout the first year of life. This article is an overview of all known data about fragility of epidermis in ‘fragile populations’: newborns, children and adolescents. It includes the recent pathological, pathophysiological and clinical data about fragility of epidermis in various dermatological diseases, such as atopic dermatitis, acne, rosacea, contact dermatitis, irritative dermatitis and focus on UV protection.

In vitro models are valuable for evaluating potential active ingredients and other molecules used in medications for atopic dermatitis (AD). However, finding appropriate in vitro models can be problematic. Our strategy was to set up different in vitro models that would mimic the pathomechanisms of AD. We describe five such models - the AD keratinocyte model, the AD reconstructed human epidermis model, the adaptive immunity model, the innate immunity model and the pruritus model - which we have used to evaluate a new ingredient for emollients derived from a biological extract. The models chosen provide useful data for the pharmacological characterization of active ingredients in adjunctive treatments for AD.

The skin is the largest organ of the body, providing a protective barrier against bacteria, chemicals and physical insults while maintaining homeostasis in the internal environment. Such a barrier function the skin ensures protection against excessive water loss. The skin's immune defence consists of several facets, including immediate, non-specific mechanisms (innate immunity) and delayed, stimulus-specific responses (adaptive immunity), which contribute to fending off a wide range of potentially invasive microorganisms. This article is an overview of all known data about fragile skin'. Fragile skin is defined as skin with lower resistance to aggressions. Fragile skin can be classified into four categories up to its origin: physiological fragile skin (age, location), pathological fragile skin (acute and chronic), circumstantial fragile skin (due to environmental extrinsic factors or intrinsic factors such as stress) and iatrogenic fragile skin. This article includes the epidemiologic data, pathologic description of fragile skin with pathophysiological bases (mechanical and immunological role of skin barrier) and clinical description of fragile skin in atopic dermatitis, in acne, in rosacea, in psoriasis, in contact dermatitis and other dermatologic pathologies. This article includes also clinical cases and differential diagnosis of fragile skin (reactive skin) in face in adult population. In conclusion, fragile skin is very frequent worldwide and its prevalence varies between 25% and 52% in Caucasian, African and Asian population.

Acne vulgaris is a skin disease affecting pilosebaceous glands in which Propionibacterium acnes (P. acnes) induced inflammation plays a central role. In order to develop new therapies against the inflammatory events, we evaluated the modulating effect of a new undecyl-rhamnoside, APRC11, on different markers of the inflammation. For this purpose, normal human keratinocytes taken from five healthy donors were pre-incubated for 24 h with APRC11 or Zinc Gluconate (Zn) which was used as reference molecule for its anti-inflammatory properties. Then, keratinocytes were stimulated with P. acnes Membrane Fraction for 6 h, in the presence of either APRC11 or Zn. Different markers were evaluated at mRNA level using a Luminex-based Quantigene array system and at protein level using an ELISA test and a Luminex array system. Results showed that P. acnes significantly increased the expression of IL-1α, IL-1RA, IL-8 and MMP-9. A 24-h treatment with APRC11 prior to the P. acnes stimulation down-regulated the P. acnes-induced cytokines over expression (IL-1α, IL-8 and MMP-9) and up-regulated IL-1RA level in a similar manner than Zn. These regulations were noted at both protein and mRNA levels. In conclusion, the new undecyl-rhamnoside APRC11 is able to down-regulate the expression of molecules implicated in cutaneous inflammation and whose expression is induced by P. acnes, confirming its potential interest in inflammatory acne.

Propionibacterium acnes has a major role in the development of acne lesions. IGF-1 stimulates the proliferation of keratinocytes via an activation of the IGF-1 receptor (IGF-1R). Zinc has been proven to work efficiently against inflammatory acne and to modulate the IGF-1 system. Our objectives were to study the modulation of IGF-1 and IGF-1R expression by P. acnes extracts and to determine their modulation by zinc gluconate. In vivo, we analyzed biopsies of acne lesions and healthy skin, and in vitro we used skin explants incubated with two P. acnes extracts-membrane fraction (MF) and cytosolic proteins-with or without zinc. IGF-1 and IGF-1R expression was evaluated using immunohistochemistry, and the IGF-1 production in supernatants was measured by ELISA. Then, IGF-1 and IGF-1R mRNA levels were analyzed using quantitative PCR on normal human epidermal keratinocytes (NHEKs). IGF-1 and IGF-1R were overexpressed in acne lesions. MF increased IGF-1 and IGF-1R expression in the epidermis of explants and was associated with an overexpression of both Ki-67 and filaggrin. Zinc had the effect of downregulating IGF-1 and IGF-1R levels. These observations were confirmed at the mRNA level for IGF-1R in NHEKs. These results demonstrate that P. acnes can induce the formation of comedones by stimulating the IGF/IGF-1R system. Moreover, zinc downregulates this pathway.

Acne vulgaris is an exceptionally common, chronic and recurring disorder affecting many adolescents and adults throughout their lifetimes. The pathogenesis of acne is multifactorial and is thought to involve excess sebum, follicular hyperkeratinization, bacterial colonization and inflammation [1]. Myrtle (Myrtus communis L., Myrtaceae) holds an important place in Western culture because of its mythological associations and its medicinal use as an antiseptic and an anti-inflammatory agent. From a phytochemical standpoint, myrtle contains unique compounds, as exemplified by a series of oligomeric nonprenylated phloroglucinols related to myrtucommulone A [2] (structure below).

Skin lesions in the allergic form of atopic dermatitis (AD) are induced by allergen-specific T cells which infiltrate the skin at the site of allergen exposure. The pathophysiology of atopic dermatitis is not entirely defined. Although Th2-type CD4+ T cells appear to be crucial in AD pathophysiology, little is known about the contribution of CD8(+) T cells in the development of the allergic skin inflammation. In the present study, we have developed a mouse model of allergen-induced AD and we have analyzed the respective roles of CD8(+) and CD4(+) T cells in the development of AD skin lesions. In sensitized mice, CD8(+) T cells are rapidly and transiently recruited to the allergen-exposed site and initiate the inflammatory process, leading to skin infiltration with eosinophils and Th1/Th2 producing cells. CDS' T cell-depleted mice show no inflammation, demonstrating that these cells are mandatory for the development of AD. In contrast, CD4+ T cell-depleted mice develop a severe form of eczema. Furthermore, adoptive transfer of CD8(+) T cells from sensitized mice into naive recipient mice leads to skin inflammation soon after allergen exposure. These data indicate that allergen-primed CD8(+) T cells are required for the development of AD-like lesions in mice. Ongoing studies may allow us to confirm these findings in humans. (C) 2007 Elsevier Masson SAS. Tous droits reserves.

The apolar fraction of the crude alcoholic extract of the sponge Euryspongia n. sp. was shown to display anti-inflammatory activity. Bioassay guided chromatographic purification led to the isolation of a known compound petrosterol (1) of 3beta-hydroxy-24-norchol-5-en-23-oic acid (2), which has never yet been found as a natural substance, and of a new steroid, 3beta-hydroxy-26-norcampest-5-en-25-oic acid (3). The absolute configurations of 2 and 3 were deduced from comparative 1H NMR data of the (S)- and (R)-phenylglycine methyl ester derivatives. These compounds were evaluated for their anti-inflammatory activity against 6-keto-prostaglandinF1alpha release in a human keratinocyte cell line HaCaT.

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 release of [(3)H]-AA from phospholipids and on the production of [(3)H]-labeled metabolites of the cyclooxygenase (CO) and 5-lipoxygenase (LO) pathways. AR was found to inhibit A23187-triggered [(3)H]-AA mobilization from phospholipids (p<0.05) and production of [(3)H]-labeled metabolites of CO (p<0.05) and LO (p<0.05) pathways. These results suggest AR decreases PLA(2)-dependent mobilization of AA from phospholipids. A closer examination of the effects of AR on prostaglandin 6KF1alpha (6KPGF1alpha), the stable metabolite of prostacyclin, revealed dose-dependent inhibition of this AA metabolite. AR also decreased A23187- and tumor necrosis factor alpha-induced cPLA(2) overexpression, as shown by cPLA(2) immunodetection and mRNA expression. These results demonstrate the high potential of AR in the treatment of inflammatory diseases of the skin.

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 human skin are potent inducers of vasodilatation, may induce pruritus and could mediate their effects via nitric oxide (NO). NO, considered as a major intra/intercellular messenger, is generated by NO synthase (NOS) enzymes identified in several cell types in the skin. NO displaying vasodilator properties are constitutively released and can also be synthesized in response to inflammatory mediators such as SP neuropeptide. The aim of the present study was first to determine whether SP, CGRP and BK were able to stimulate NO release from human endothelial cells (HECs); the second objective was to induce neurogenic inflammation on HECs with SP (10–100 pm) and to evaluate the activity of Avena Rhealba® oatmeal – Roasting extract – (0.001–0.005%) on endothelial NOS (eNOS) mRNA expression by RT‐PCR. Avena Rhealba® significantly inhibits endothelial cells substance P‐induced expression of eNOS. Our results demonstrate the regulator properties of Avena Rhealba® with respect to neurogenic inflammatory response showing therefore a real interest of Avena Rhealba® in atopic dermatitis inflammatory pathology.