Increased Activity and Number of Epidermal Melanocytes in Lesional Psoriatic Skin.

BACKGROUND: Psoriatic lesions may resolve with hypo- or hyperpigmentation. The involvement of melanocytes in this dichotomous clinical outcome is not fully investigated. OBJECTIVES: Qualitative and quantitative assessment of melanocytes in untreated lesional and non-lesional psoriatic skin (n = 15) and healthy controls (n = 10). METHODS: Skin biopsies were labelled immunohistochemically (APAAP technique) with the antimelanocyte monoclonal antibodies (MoAbs) HMB45, Melan A, tyrosinase and microphthalmia-associated transcription factor (MITF). The labelled melanocytes were evaluated by an independent investigator with a digital image analyser. RESULTS: Lesional melanocytes, in contrast to those in non-lesional and healthy skin, exhibited features of activation in the form of dilatation, prominent and long dendrites and intense labelling. The number of melanocytes was significantly increased in psoriatic lesions in comparison with non-lesional psoriatic and healthy skin as shown by counts of cells labelled with the MoAbs HMB45 (3-fold; p < 0.001), Melan A (1.6-fold; p < 0.01) and tyrosinase (1.5-fold; p < 0.01). In contrast, labelling with MITF revealed no significant difference (1.2-fold increase; p > 0.05). Likewise, no significant difference between non-lesional psoriatic and healthy skin control was found (p > 0.05). Furthermore, no positively labelled dermal cells were detected, apart from few only detected with Melan A. CONCLUSIONS: Epidermal melanocyte activity and numbers are increased in the epidermal compartment of psoriatic lesions providing an explanation for postinflammatory hyperpigmentation.

Stress and serum TNF-alpha levels may predict disease outcome in patients with pemphigus: a preliminary study.

The aim of the current preliminary case-control study was to estimate the initial serum levels of tumor necrosis factor alpha (TNF-alpha) in case patients with pemphigus vulgaris (PV) and pemphigus foliaceus (PF) and correlate them with history of stress, body surface area (BSA) affected, disease severity, and disease outcome. Ten PV and 4 PF case patients as well as 7 healthy matched controls had their serum levels of TNF-alpha measured by an enzyme-linked immunosorbent assay. Case patients were treated and followed up for 2 months. A statistically significant elevation in serum levels of TNF-alpha in PV case patients compared with controls and in PV case patients compared with PF case patients was detected (P < .05), with no significant difference between PF case patients and controls (P > .05). No significant correlation was detected between the serum levels of TNF-alpha and the BSA affected (P > .05). Four PV case patients had a bad disease outcome, of which 3 had severe emotional stress a month prior to the onset of the attack. All 4 showed significantly elevated initial serum levels of TNF-alpha compared with those who had a good disease outcome (P < .05). Emotional stress is a factor affecting prognosis of the disease. Pretreatment assessment of serum TNF-alpha levels in patients with pemphigus may be a guide to the expected prognosis and selection of the proper treatment regimen.

Aesthetic aspects of skin aging, prevention, and local treatment.

Skin aging is a complex biologic process influenced by a combination of intrinsic and extrinsic factors. Aging skin shows wrinkles, uneven tone, loss of elasticity, and thinning. Skin health is considered one of the principal factors representing overall well-being and the perception of health in humans; therefore, anti-aging strategies to combat aging signs and dysfunction have been developed over the last decades. Understanding the mechanism behind skin aging is required for elucidation of the mechanism of action and, hence, the potential benefits of the claimed anti-aging products. In this review, preventive measurements, cosmetologic strategies, and photoprotection (systemic antioxidants, ultraviolet and filters), as well as the mechanisms of action and the effectiveness of topical pharmaceutical agents, such as antioxidants (vitamins, polyphenols, and flavonoids) and cell regulators (retinols, peptides, hormones, and botanicals), are presented.

Age influences the skin reaction pattern to mechanical stress and its repair level through skin care products.

Skin aging is associated with alterations of surface texture, sebum composition and immune response. Mechanical stress induces repair mechanisms, which may be dependent on the age and quality of the skin. The response to mechanical stress in young and aged individuals, their subjective opinion and the objective effectiveness of skin care products were evaluated by biophysical skin quality parameters (stratum corneum hydration, transepidermal water loss, skin pH, pigmentation and erythema) at baseline, 1, 6, 24h and 7days at the forearms of 2 groups of healthy volunteers, younger than 35 years (n=11) and older than 60 years (n=13). In addition, casual surface lipid composition was studied under the same conditions at the baseline and day 7 after mechanical stress induction. Evaluations were also performed in stressed skin areas treated daily with skin care products and the subjective opinion of the volunteers was additionally documented. The tested groups exhibited age-associated baseline skin functions as well as casual surface lipid composition and different reaction patterns to mechanical stress. Skin care was more effective in normalizing skin reaction to stress in the young than in the aged group. The subjective volunteer opinion correlated with the objective measurements.

Age-associated skin changes in innate immunity markers reflect a complex interaction between aging mechanisms in the sebaceous gland.

Skin aging is the most apparent form of senescence and could reflect the aging of inner organs. Molecular changes involved in innate immunity signaling, tumorigenesis, and inflammation were studied. Protein levels were evaluated based on the immunohistochemistry of the skin of 42 young and old individuals. The investigated molecules (peroxisome proliferator-activated receptors-α and -γ, Toll-like receptor 4, and interleukin-6 and 8) were expressed in almost all skin compartments and exhibited significant aging-associated downregulation in epithelial tissues, mostly in the sebaceous glands, the sweat glands, and the epidermis. With the exception of interleukin-6 in the dermal tissue, no upregulation was detected in the aged group. The results obtained indicate an interesting interaction between different pathways of aging, namely defective stress responses, downregulated innate immunity responses, and activation of the tumorigenesis pathway, which was especially apparent in the sebaceous glands.

Neuropeptides and skin aging.

Abstract Neuropeptides (NP) are peptides that are released as chemical messengers from nerve cells. They act either in an endocrine manner, where they reach their target cells via the bloodstream or a paracrine manner, as co-transmitters modulating the function of neurotransmitters. To date approximately 100 different NP have been described in the literature. In recent years, several studies have documented that human skin expresses several functional receptors for NP, such as corticotropin-releasing hormone, melanocortins, ß-endorphin, vasoactive intestinal polypeptide, neuropeptide Y and calcitonin gene-related peptide. These receptors modulate the production of inflammatory cytokines, proliferation, differentiation, lipogenesis and hormone metabolism in human skin cells. In addition, several NP are directly produced by human skin cells, indicating the complexity of understanding the real functions of NPs in human skin. In this review we address the possible effects of neuropeptides on the pathogenesis of aged skin.

Aging-related changes in cutaneous corticotropin-releasing hormone system reflect a defective neuroendocrine-stress response in aging.

BACKGROUND AND OBJECTIVE: Skin, being a mirror of the body, is a major target for aging research. Aging is a complex process that involves the decline of function or dysfunction of many systems. The corticotropin-releasing hormone (CRH) system is involved in skin inflammation. In addition, CRH has a suggested role in age-associated conditions and in animal aging models. However, a consistent logic interaction between the different CRH system components and the aging process has, to our knowledge, never been examined before. METHODS: The expression of CRH, CRH-binding protein (CRHBP), CRH receptor 1 (CRHR1), and CRH receptor 2 (CRHR2) in healthy skin samples of 42 patients of different ages (18-92 years) was evaluated by immunohistochemistry, and the age-related changes were assessed. RESULTS: Compared with young skin, the aged skin displayed an upregulation of CRH in sebaceous glands and CRHR1 in hair follicles and the epidermis. Moreover, age-associated downregulation of CRHBP in the sebaceous and sweat glands was detected, whereas the CRHR2 showed no age-related changes. CONCLUSION: Our findings suggest that the age-associated changes in the expression of CRH system components reflect an exaggerated stress response reaction, putting the aged skin continuously in a stress-like situation.

Identification of biomarkers of human skin ageing in both genders. Wnt signalling - a label of skin ageing?

The goal of our work has been to investigate the mechanisms of gender-independent human skin ageing and examine the hypothesis of skin being an adequate model of global ageing. For this purpose, whole genome gene profiling was employed in sun-protected skin obtained from European Caucasian young and elderly females (mean age 26.7±4 years [n1 = 7] and 70.75±3.3 years [n2 = 4], respectively) and males (mean age 25.8±5.2 years [n3 = 6] and 76±3.8 years [n4 = 7], respectively) using the Illumina array platform. Confirmation of gene regulation was performed by real-time RT-PCR and immunohistochemistry. 523 genes were significantly regulated in female skin and 401 genes in male skin for the chosen criteria. Of these, 183 genes exhibited increased and 340 decreased expression in females whereas 210 genes showed increased and 191 decreased expression in males with age. In total, 39 genes were common in the target lists of significant regulated genes in males and females. 35 of these genes showed increased (16) or decreased (19) expression independent of gender. Only 4 overlapping genes (OR52N2, F6FR1OP2, TUBAL3 and STK40) showed differential regulation with age. Interestingly, Wnt signalling pathway showed to be significantly downregulated in aged skin with decreased gene and protein expression for males and females, accordingly. In addition, several genes involved in central nervous system (CNS) ageing (f.i. APP, TAU) showed to be expressed in human skin and were significanlty regulated with age. In conclusion, our study provides biomarkers of endogenous human skin ageing in both genders and highlight the role of Wnt signalling in this process. Furthermore, our data give evidence that skin could be used as a good alternative to understand ageing of different tissues such as CNS.