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Psoriasis is a multifactorial disease that involves genetic, immunological and environmental factors. During the last decade, several studies by genome scan on families or cases/controls helped to highlight more than ten loci "PSORS" located on different chromosomes and containing several candidate genes. Psoriasis appears as a genetic disease that follows the mixed model with the involvement of a major gene (PSORS1) and a set of minor genes with a variable penetrance depending on the locus. Genetic data have focused on the involvement of the immune system in the pathogenesis of psoriasis. It is now accepted that psoriasis is an immunological disease involving the response profiles TH1 and TH17. Much remains to be done to better elucidate the mechanisms involved in the genesis of psoriatic lesions to find new therapeutic targets., (Copyright © 2013. Published by Elsevier SAS.)

The occurrence of hyperpigmentation during chemotherapy is one of the most frequent dermatological adverse events observed with these drugs. It may arise with numerous anticancer agents, and can be either localized or diffuse, occurring either immediately or after inflammatory dermatological lesions. Nails, mucosa and skin may all be affected. Though the incidence is high in clinical practice, such drug-induced hyperpigmentation has been only rarely individualized and characterized. Herein we describe the main clinical, histological and pathophysiological characteristics of these lesions and the most frequently incriminated chemotherapeutic agents, as well as the anatomical areas involved and the most specific clinical patterns such as flagellate dermatitis, reticulate or serpentine supravenous hyperpigmentation and eruptive naevi., (Copyright © 2012 Elsevier Masson SAS. All rights reserved.)

Aim: To analyze the effects of PRF (a platelet and immune autologous concentrate) on in vitro proliferation of human keratinocytes and preadipocytes, and to determine if these results may offer an opening on new clinical investigations, particularly in the improvement of tympanoplasties and facial lipostructures (Coleman's technique)., Materials and Methods: Human tympanic keratinocytes and preadipocytes are collected and cultured using the explant technique. 4 series of each type of cells are cultivated either in normal condition (control group) or with PRF (test group). The Petri dishes (of culture) are taken out on the 3rd, 7th, 14th and 21st day, for counting. Evolutions of cells' number are analyzed with a variance test., Results: The number of cells in culture increases of more than 60% on the 7th day, and of almost 150% right from the 14th day when in presence of PRF. The daily proliferation peak occurs around the 14th day. The two cellular tested types react similarly., Conclusion: The PRF, considered as a healing biomaterial, could be used in tympanic and facial lipostructures surgeries, in order to improve the therapeutic result. Other applications in microsurgery and in plastic surgery may be possible, but specific clinical studies need to validate such protocols.

Toll receptors were first identified as an essential molecule for embryonic patterning in Drosophila and were subsequently shown to be a key in antibacterial and antifungal immunity in adult flies. Toll receptors have been conserved throughout evolution. In mammals, TLRs have been implicated in both inflammatory responses and innate host defense to pathogens. The 11 different TLRs recognize conserved molecular patterns of microbial pathogens termed pathogen-specific molecular patterns (PAMPs), that permit to confer responsiveness to a wide variety of pathogens. Endogenous ligands are also able to activate TLRs. All adult tissue is capable to express at least one of member of TLR family, but a largest repertoire of TLRs is found in tissues exposed to the external environment. The TLR activation induce the NF-kappaB translocation to the nucleus and cytokine secretion. Since the primary function of skin is to provide an effective barrier against outside agression, it is likely that keratinocytes may play a role in a rapid and efficient host defence system, and the fact that keratinocytes are capable of expressing a wide variety of TLRs is subsequently not surprising.

Vulvar melanosis is a benign disorder that may suggest a malignant melanoma. We report the case of a woman in whom partial vulvectomy was performed to eradicate the melanotic macule. The lesion corresponds to increased accumulation of melanin inside keratinocytes in the absence of any melanocytic neoplasm.

The concept of neuro-immuno-cutaneous system (NICS) means narrow interrelations between nervous system, immunity and skin. Indeed, there are numerous cellular contacts between nerve fibers, cutaneous cells and immune cells; cutaneous cells can synthesize neuromediators and they express receptors to these molecules; neuromediators are able to modulate functions of cutaneous and/or immune cells. Using confocal or electron microscopy, connexions between nerve fibers and cutaneous cells have been observed. In the skin, nerve fibers may secrete neuromediators: substance P, vaso-active intestinal peptide (VIP), somatostatin, calcitonin-gene related peptide (CGRP), gastrin-releasing peptide (GRP), neuropeptide Y, peptide histidine-isoleucine (PHI), neurotensin, neurokinins A et B, bradykinin, acetylcholine, catecholamines, endorphins and enkephalins. Neurohormones such as prolactin, melano-stimulating hormone (MSH) or adreno-corticotrophic hormone (ACTH) are also expressed in the skin. Neuromediators and neurohormones are also secreted by cutaneous cells and these cells express receptors. Functions of epidermal or dermal cells are modulated by these substances. Immune cells transiently present in the skin (macrophages, lymphocytes...) are modulated by neuromediators through receptors. In the course of skin diseases, especially inflammatory diseases, the NICS is destabilized. Psoriasis and atopic dermatitis are good examples. This phenomenon might be due to inflammation but is also responsible for induction and maintenance of the inflammation.

Lipid peroxidation has been implicated in skin damage by ultraviolet radiation. The aim of the study was to determine the kinetic of lipid peroxidation induced by ultraviolet beta (UVB) in adult keratinocytes and fibroblasts in culture. The keratinocytes were obtained from a single primary culture and the fibroblasts were in the same subculture (4 to 10 transfers). For UVB irradiation, the cells were maintained in a small volume of Hanks balanced salt solution and were irradiated (0.75, 1.5, 3 and 4.5 Jcm-2). Then cells were cultured for 3 to 48 hours. Lipid peroxidation was estimated by free MDA determination in both extracellular medium and cells using a size exclusion chromatography coupled to an HPLC procedure. In addition, LDH release in culture media was evaluated as in indice of cytotoxicity. An increase of total free MDA was observed 3 hours after cell irradiation which was dose-dependent from 0.75 to 3 Jcm-2 for keratinocytes and fibroblasts. MDA was detected both in cells and in culture media. As soon as 3 hours after irradiation 90% in total MDA was present in the culture media. Kinetic of lipid peroxidation: for 0.75 Jcm-2, an elevation of MDA was observed 12 hours after irradiation in both cultures. A further increase in MDA was noted 24 hours after fibroblasts irradiation but not in irradiated keratinocytes. LDH release in culture media increased with post irradiation time until 48 hours. The cytotoxic effect of UVB irradiation on keratinocytes and fibroblasts cultures was shown by an enhancement of lipid peroxidation which was detectable during 48 hours after irradiation. An increase of LDH release was observed simultaneously.

In inflammatory dermatoses, adhesion molecules are involved in the interaction of leukocytes with endothelial cells, extra-cellular matrix and epidermal cells. In dermatosis where epidermal cells are the main targets of inflammation, the keratinocytes are activated and participate to the local immune reaction through the secretion of cytokines and the expression of the adhesion molecule ICAM-1 and the HLA-DR antigens. Induction of ICAM-1 by IFN gamma or TNF alpha on keratinocytes that do not express this molecule in normal skin may account for the recruitment of T cells into the epidermis. In the dermis, an up-regulation of ICAM-1 expression occurs on endothelial cells activated by cytokines (IL-1, TNF alpha...) and is usually correlated with an induction of ELAM-1 and less frequently VCAM-1. These adhesion molecules are involved in the recruitment of inflammatory cells but also in the control of their retention and migration through the skin.

We have investigated the non-androgenic factors that induce the prostatic buds from the sinus epithelium. The buds were found to be induced in the explants cultured in the androgen-deficient medium containing 20 ng/ml rat keratinocyte growth factor (KGF) irrespective of the sex of the sinus.

Many biological events involve an initial stage of adhesion. The molecules that are responsible for the process of adhesion have been studied extensively in recent years. The most widespread receptors taking part in cell-external matrix and cell-cell reactions are from the families of integrins and immunogloblins. In normal skin, the keratinocytes and fibroblasts essentially express beta 1 (VLA) receptors and the cells of Langerhans the beta 2 receptors of the integrin family. Their pathological modification is under study. In contrast, involvement of the ICAM-1 molecule (ligand of receptor LFA-1) in pathology seems to be considerable. ICAM-1 is expressed by keratinocytes in many benign and malignant skin diseases and this makes possible interaction with LFA-1 lymphocytes. The passage of lymphocytes towards the epidermis is the basis of all inflammatory and immune reactions and is dependent on adhesion molecules. It will doubtless, in the future, be possible to explain the physiopathology of inflammatory skin reactions in terms of excessive expression or insufficient ICAM-1 by pathological keratinocytes.

The purpose of this study was to determine tissue distribution of certain cytokeratins along the ectocervical lining. A series of 20 cases was investigated by immunocytochemical labelling with specific antibodies against cytokeratins 19, 18, 8, 7, 10. Monoclonal antibodies were used on frozen sections. Distribution of keratin or alteration in expression was correlated with morphologic changes. All specimens were lined by a normal stratified squamous epithelium which was devoid of argyrophilic cells. Low molecular weight cytokeratins 8, 18, 19 (normally expressed in simple epithelia) were consistently and exclusively expressed through out the basal cell layer of the ectocervical lining. Some other particular immunostainings have been noted. A peculiar staining pattern was observed around some stromal papillae. Development of papillae was accompanied by the expression of cytokeratin 10 (which is commonly detected in skin), and by a reduction in the level of expression of simple epithelial cytokeratins. In addition, in the middle zone, anticytokeratin 10 revealed a mosaic of positive and negative cells even in light microscopically non keratinizing squamous epithelium, with differences of expression from case to case.

Epidermal cells produce IL-1 and contra IL-1 which respectively stimulate and decrease fibroblast proliferation. In order to get better insight into the nature of keratinocyte-fibroblast interactions, we have analyzed the effect of soluble factors produced by unstimulated normal human keratinocytes and keratinocyte cell lines on the proliferation of normal human dermal fibroblasts. The results were compared to these obtained with human recombinant IL-1 and IL-2. We observed that: 1) normal keratinocytes (monolayers or stratified) released in the culture medium a factor stimulating fibroblast proliferation by 45 to 160%; 2) supernatants of unstimulated PAM 212 keratinocyte cell line also contained the stimulatory activity; 3) addition of IL-1 beta to the culture medium at concentration ranging from 0.1 to 1.000 U/ml induced a dose-dependent increase in fibroblast proliferation, whereas IL-2 was ineffective; 4) gel filtration analysis (ACA 54) of serum-free supernatant showed that the activity could be eluted from 3 peaks (Mw ranging from 10 to 20 kD). The present data show that unstimulated normal human keratinocytes produce soluble factor(s) (maybe related to IL-1) which stimulate human dermal fibroblast proliferation and which could be of major importance in the modulation of fibroblast metabolism, in vivo.