Increase In Number Of Melanocytes Research Articles

Decrypting the Potential of Nanotechnology-Based Approaches as Cutting-Edge for Management of Hyperpigmentation Disorder.

The abundant synthesis and accretion of melanin inside skin can be caused by activation of melanogenic enzymes or increase in number of melanocytes. Melasma is defined as hyperpigmented bright or dark brown spots which are symmetrically distributed and have serrated and irregular borders. The three general categories of pigmentation pattern include centro facial pattern, malar pattern, and mandibular pattern. Exposure to UV rays, heat, use of cosmetics and photosensitizing drugs, female sex hormonal therapies, aberrant production of melanocyte stimulating hormone, and increasing aesthetic demands are factors which cause the development of melasma disease. This review gives a brief overview regarding the Fitzpatrick skin phototype classification system, life cycle of melanin, mechanism of action of anti-hyperpigmenting drugs, and existing pharmacotherapy strategies for the treatment of melasma. The objectives of this review are focused on role of cutting-edge nanotechnology-based strategies, such as lipid-based nanocarriers, i.e., lipid nanoparticles, microemulsions, nanoemulsions, liposomes, ethosomes, niosomes, transfersomes, aspasomes, invasomes penetration-enhancing vesicles; inorganic nanocarriers, i.e., gold nanoparticles and fullerenes; and polymer-based nanocarriers i.e., polymeric nanoparticles, polymerosomes, and polymeric micelles for the management of hyperpigmentation.

Immuno-Histochemical and Quantitative Study of Melanocytes and Melanin Granules in Oral Epithelial Dysplasia.

Oral Epithelial dysplasia (OED) is a potentially malignant disorder that is characterized by the presence of architectural and cytological changes. One of the prime factors responsible for the development of these lesions is the usage of tobacco. A variety of factors provide protective mechanism in order to prevent the effects of chemotoxic agents including tobacco products of which, melanin pigmentation is one of the vital elements. Role of melanocytes in progression of OED has remained unclear, so the present study was done to evaluate density of melanocyte and melanin granules in different grades of epithelial dysplasia and to correlate both findings with different grades of epithelial dysplasia. The study included 60 OED cases, of which three histopathogical sections were prepared from each block. The sections were stained with Hematoxylin and Eosin, Masson Fontana and Human Melanoma Black (HMB-45), an immunohistochemical stain. Quantification of melanin granules was evaluated under 40X magnification using arbitrary scale with micrometer square as, 0= Absence of melanin granules, 1= Rare and scattered melanin granules, 2= Dense but not aggregated melanin granules, 3= Dense and aggregated melanin granules. Density of melanocytes was evaluated under 10X magnification. Five consecutive fields were evaluated for melanocytes and melanin granules starting from the field of highest density. There was an insignificant increase in number of melanocytes and melanin granules in mild and moderate dysplasia compared to normal but significant reduction was observed in severe dysplasia. The decrease in number of melanocytes and melanin granules was proportional to severity of epithelial dysplasia. This could be due to chronic irritation by chemical products leading to death of melanocytes.

A morphometric and immunohistochemical study of melanocytes in periorbital hyperpigmentation.

An increase in number of melanocytes in the basal cell layer of the epidermis is an important feature in many disorders of hyperpigmentation. In this study, we attempted an objective evaluation of the linear density of melanocytes and keratinocytes, along with other epidermal characteristics, in periorbital hyperpigmentation using immunohistochemistry and morphometric techniques. Melanocytes and epidermal parameters were assessed by digital morphometry in 30 newly diagnosed cases of periorbital hyperpigmentation and 14 controls from the post-auricular region. Melanocytes were labelled with the immunohistochemical stains, Melan-A and tyrosinase. We studied the linear keratinocyte density, mean linear melanocyte density, ratio of melanocytes to keratinocytes, the ratio between inner and outer epidermal length, maximum epidermal thickness and minimum epidermal thickness. Melan-A expression of melanocytes showed strong positive correlation (r=0.883) with the tyrosinase expression. Mean linear melanocyte density was 24/mm (range: 13-30/mm) in cases and 17/mm (13-21/mm) in controls and this difference was statistically significant (P<0.001). The mean ratio of melanocyte to keratinocyte was 0.22 (0.12-0.29) in cases and 0.16 (0.12-0.21) in controls; again, this difference was statistically significant (P<0.001). There was a mild negative correlation with linear keratinocyte density (r=-0.302) and the ratio between inner and outer epidermal length (r=-0.456). However, there were no differences in epidermal thicknesses. There were fewer control biopsies than optimal, and they were not taken from the uninvolved periorbital region. Mean linear melanocyte density and the ratio of melanocytes to keratinocytes is increased in cases with periorbital hyperpigmentation. It is, therefore, likely that increased melanocyte density may be the key factor in the pathogenesis of periorbital hyperpigmentation.

IL-17 and TNF Synergistically Modulate Cytokine Expression while Suppressing Melanogenesis: Potential Relevance to Psoriasis

Inflammation-associated pigmentation changes are extremely common, but the etiology behind this clinical observation remains elusive. Particularly, it is unclear how the myriad of cytokines known to be involved in inflammatory skin processes affect epidermal melanocytes. We sought to determine how IL-17 and TNF influence normal human melanocytes, as these two cytokines have been implicated in various skin diseases. IL-17 and TNF jointly stimulated broad inductions of cytokines , including melanoma mitogens CXCL1 and IL-8. Moreover, IL-17 and TNF synergistically inhibited pigmentation-related signaling and melanin production, and induced keratinocytes production of β-defensin 3, an antagonist for melanocortin-receptor 1. When analyzing psoriasis lesions that are known to over express IL-17 and TNF, we observed an increase in melanocyte number and a simultaneous decrease in pigmentation signaling. Furthermore, therapeutic neutralization of TNF and IL-17 with mAbs results in a rapid recovery of pigment gene expression in psoriasis lesions. These results demonstrate that IL-17 and TNF can impact both the growth and pigment production of melanocytes, which may contribute to the pigmentation changes associated with psoriasis. These findings may allow the development of novel therapeutics for pigmentary disorders and bring new insights into the immune milieu surrounding melanocytes and related neoplasms.

An integrated model for melanocyte‐specific gene expression and melanogenesis

AbstractThe steady increase in the incidence of cutaneous (skin) malignant melanoma worldwide generates the necessity to understand the key molecular events underlying melanogenesis and melanoma. Melanogenesis has two main stages: immediate pigmentation occurs through the redistribution of pigment‐containing melanosomes to the dendrites of melanocytes, and subsequently to the surrounding keratinocytes, without the need for any new melanin synthesis. The effect is therefore subtle and transient. Delayed and sustained tanning, however, requires (a) an increase in melanocyte number and dendricity, (b) an increase in melanosome number, and (c) an increase in melanin content. This computer‐based model focuses on the sustained eumelanin (black/brown pigment) production through melanocyte‐specific gene expression in response to external stimulus. We find in our model that high levels of melanin can be reached within an hour of stimulation. Furthermore we successfully show metabolic downregulation of pigment synthesis through employing in our simulations an experimentally‐described inhibitor for melanogenic enzymes. We see this model as a starting point for in silico drug screening for skin lightening agents, sun‐tanning agents, and eventually for anti‐melanoma agents that are under development.

Review: ligands for receptor tyrosine kinases expressed in the skin as environmental factors for melanocyte development.

Skin is the major tissue where melanocytes develop, and skin keratinocytes provide the necessary micro-environment for melanocyte survival, proliferation, differentiation, and migration. In this paper, we will discuss the ligands for receptor tyrosine kinases produced as environmental cues to support melanocyte development in the skin.

Lentiginous macules and patches of neurofibromatosis (an approach to better terminology).

Freckles (ephelides) are small, light brown macules of sun-exposed areas in fair-skinned subjects. On the other hand, freckle-like pigmentation of the axilla is a highly characteristic feature of neurofibromatosis. To what extent (clinically and pathologically) are the two pigmentary defects similar? And to what extent are café-au-lait patches and freckle-like lesions similar pathologically? Ten cases of neurofibromatosis and 10 cases of freckles were examined clinically. Two biopsies were taken from the former; one obtained from an axillary freckle-like lesion, and the other from a café-au-lait patch. One biopsy only was taken from freckles. The biopsies were processed for haematoxylin and eosin, silver stain and transmission electron microscopy. Obvious differences were detected between freckles (ephelides) and freckle-like lesions in cases of neurofibromatosis. Café-au-lait patches and freckle-like lesions showed the same pathological changes of lentigo simplex, with increased melanin pigment from the basal layer up to the stratum corneum, moderate elongation of the rete ridges and mild inflammatory infiltrate intermingled with melanophages. Electron microscopy revealed an increase in melanocyte number and the presence of giant melanin granules in freckle-like pigmentation as well as café-au-lait patches. These ultrastructural freckles (ephelides) showed an increase in activity but not the number of melanocytes. The term freckle-like should be changed to lentiginous macules of neurofibromatosis. On the other hand, the café-au-lait patches should be considered as lentiginous patches. Freckles should be restricted to sun-exposed areas in fair-skinned persons only.

Multinucleated Melanocytes on Sun-Damaged Skin Suggest Malignancy

Distinguishing the lentigo maligna (LM) type of melanoma in situ from excessively sun-damaged skin with increased numbers of melanocytes is often very

Endothelin 3 promotes neural crest cell proliferation and mediates a vast increase in melanocyte number in culture.

Mutations in the endothelin 3 (EDN3) gene severely affect the development of neural crest-derived melanocytes. In this paper, we report the action of EDN3 on neural crest cells in vitro. The presence of EDN3 leads to a large increase in the number of cells, the majority of which eventually differentiate into melanocytes that aggregate to form a reproducible pigmentation pattern. Quantitative analysis of the effect of different culture conditions revealed that EDN3 initially promotes neural crest cell proliferation. This phase of expansion, which can be prolonged for a few weeks if the cells are replaced regularly, is followed by both a decrease in cell proliferation and the onset of melanocytic differentiation. Therefore, EDN3 is a potent mitogen for early neural crest cell precursors that can give rise to melanocytes.

Effects of Biologically Active Tumour‐Promoting and Non‐Promoting Phorbol Esters on In Vitro Growth of Melanocytic Cells

Sapintoxin A (SAP A), a naturally occurring biologically active but non-promoting phorbol ester, acts as an effective in vitro mitogen for freshly derived human melanocytes. Seven days after addition of 50 nM SAP A there was a four to fivefold increase in melanocyte number over that observed in untreated control cultures comparable to that achieved with a 50 nM concentration of 12-0-tetradecanoylphorbol 13-acetate (TPA). The fluorescent stage 2 promoter sapintoxin D (SAP D) also supported the growth of these cells, with a 50 nM dose producing an increase in cell number comparable to that observed with 200 nM TPA. Similar results were obtained with an established, but non-tumorigenic, line of murine melanocytes. The same compounds exerted a potent anti-proliferative effect against transformed melanocyte lines of murine and human origin associated with morphological alterations and an increase in melanin production consistent with induced cytodifferentiation.

The Effect of Sunlight on Human Epidermis

Qualitative as well as quantitative studies, including direct counting of cells and linear scanning of electron micrographs, to determine volume ratios for epidermal dendritic cells revealed an increase in melanocyte number and an essential absence of Langerhans' cells following two weeks of daily ultraviolet irradiation. These findings suggest some form of relationship between the melanocyte and the Langerhans' cell.