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1.
Interactions between melanocytes and keratinocytes in the skin suggest bi‐directional interchanges between these two cell types. Thus, melanocytes cultured alone may not accurately reflect the physiology of the skin and the effects of physiological regulators in vivo, because they do not consider possible interactions with keratinocytes. As more and more pigment genes are identified and cloned, the characterization of their functions becomes more of a challenge, particularly with respect to their roles in the processing and transport of melanosomes and their transfer to keratinocytes. Immortalized melanocytes mutant at these loci are now being routinely generated from mice, but interestingly, successful co‐culture of murine melanocytes and keratinocytes is very difficult compared with their human counterparts. Thus, we have now optimized co‐culture conditions for murine melanocytes and keratinocytes so that pigmentation and the effects of specific mutations can be studied in a more physiologically relevant context. 相似文献
2.
In mammalian skin, melanocyte proliferation and melanogenesis can be stimulated by keratinocytes, fibroblasts and other regulatory factors. To determine whether hydroxybenzyl alcohols (HBAs) show more inhibitory in melanocytes cultured alone or in melanocytes co-cultured with keratinocytes, we developed a murine melanocyte-keratinocyte co-culture model to investigate the pigmentation regulators in company with other melanogenic inhibitors and stimulators. It was found that the effects of HBAs and melanogenic factors were more evident in melanocytes co-cultured with keratinocytes. Keratinocytes may play a synergistic role in melanocyte melanogenesis and influence the pigment production. The tests in the co-culture model also imply that the inhibitory effects of HBAs on melanogenesis are due to the direct inhibition of melanosomal tyrosinase activity. HBAs showed a low cytotoxicity. The eventual results proved that HBAs are promising and safe agents for skin whitening in melanocyte alone and in co-culture systems. The co-culture model provides a more physiologically realistic condition to study the interaction between melanocytes and keratinocytes, which enables a reliable screening system for depigmenting compounds. 相似文献
3.
Szu-Hsiu Liu I-Ming Chu I-Horng Pan 《Journal of enzyme inhibition and medicinal chemistry》2013,28(4):526-534
In mammalian skin, melanocyte proliferation and melanogenesis can be stimulated by keratinocytes, fibroblasts and other regulatory factors. To determine whether hydroxybenzyl alcohols (HBAs) show more inhibitory in melanocytes cultured alone or in melanocytes co-cultured with keratinocytes, we developed a murine melanocyte–keratinocyte co-culture model to investigate the pigmentation regulators in company with other melanogenic inhibitors and stimulators. It was found that the effects of HBAs and melanogenic factors were more evident in melanocytes co-cultured with keratinocytes. Keratinocytes may play a synergistic role in melanocyte melanogenesis and influence the pigment production. The tests in the co-culture model also imply that the inhibitory effects of HBAs on melanogenesis are due to the direct inhibition of melanosomal tyrosinase activity. HBAs showed a low cytotoxicity. The eventual results proved that HBAs are promising and safe agents for skin whitening in melanocyte alone and in co-culture systems. The co-culture model provides a more physiologically realistic condition to study the interaction between melanocytes and keratinocytes, which enables a reliable screening system for depigmenting compounds. 相似文献
4.
KEIKO NAKAZAWA HISAYOSHI NAKAZAWA CHRISTIAN COLLOMBEL ODILE DAMOUR 《Pigment cell & melanoma research》1995,8(1):10-18
Active roles of cell-cell interaction between melanocytes and neighboring keratinocytes for the regulation of melanocyte functions in the skin have been suggested. We examined substantial regulatory mechanisms of keratinocyte extracellular matrix (kECMs) for normal human melanocyte functions without direct cell-cell contact. We specially devised kECMs from proliferating or differentiating keratinocytes and further treated them with environmental stimulus ultraviolet B (UVB) for skin pigmentary system. Normal human melanocytes (NHM) were cultured on the various keratinocyte ECMs and initially the effects of the kECMs upon melanocyte morphology (dendrite formation and extension), growth, melanin production and expressions of pigmentation-associated protein (MEL-5) and proliferation-associated protein (proliferating cell nuclear antigen; PCNA/cyclin) were studied. Then we compared the effects of these cell-matrix interactions with those of direct melanocyte-keratinocyte, cell-cell contact in co-culture on melanocyte functions. Melanocytes cultured on any types of the kECMs that were tested significantly extended dendrites more than that on plastic cell culture dish without kECM (control). Melanocytes cultured on the kECM prepared from UVB irradiated differentiating keratinocytes resulted in 219% increase in the number of dendrites. The growth of melanocytes on kECMs was also stimulated up to 280% of control. The kECM produced by proliferating keratinocytes had a more significant effect on the growth than kECM from differentiating keratinocytes. This melanocyte growth stimulating effect was decreased with kECM from UVB treated differentiating keratinocytes. The melanin content per melanocyte was constant on any of the kECMs. Expression of pigmentation-associated protein detected by monoclonal antibody, MEL-5, was not changed on the kECM, while it was increased in melanocytes in co-culture with keratinocytes. Expression of PCNA/cyclin in melanocytes cultured on kECMs was generally downregulated on kECM and in co-culture compared to that in a control culture. We demonstrated that the kECMs play important roles in the melanocyte morphology and proliferation. These observations suggest that environmental (UVB) and physiological (Ca++) stimuli can regulate melanocyte functions through the keratinocyte extracellular matrix in vivo. 相似文献
5.
Youn-Ho Shin Young-Kwon Seo Hee-Hoon Yoon Kye-Yong Song Jung-Keug Park 《Biotechnology and Bioprocess Engineering》2012,17(1):203-210
Melanocytes are the melanin-producing cells by melanogenesis, and the pigment melanin is primarily responsible for the color
of skin. These cells contain dendrites that are in close contact with neighboring keratinocytes. Keratinocytes produce and
secrete factors that regulate the proliferation and melanogenesis of melanocytes in vitro. Therefore, adopting only melanocyte pure culture may not clearly reflect the skin physiology in vivo. In this study, we applied a two-culture model using melanocytes and keratinocytes from human skin, such as melanocyte pure
culture and melanocyte co-culture with keratinocyte. And then, there was compared the responses of melanocytes under different
culture conditions (treatment with arbutin, MSH-α and UV-B irradiation). The results show that there was no significant difference
in melanocyte proliferation and melanogenesis between arbutin and MSH-α treatment. However, the co-culture model was more
stable than the pure culture model in terms of melanocyte proliferation and melanogenesis upon UV-B irradiation. Therefore,
the co-culture model was superior to the pure culture as a useful method for the study of melanocytes and epidermal melanin
unit. 相似文献
6.
Y Yoshida-Amano A Hachiya A Ohuchi GP Kobinger T Kitahara Y Takema M Fukuda 《PloS one》2012,7(7):e41160
Human skin color is predominantly determined by melanin produced in melanosomes within melanocytes and subsequently distributed to keratinocytes. There are many studies that have proposed mechanisms underlying ethnic skin color variations, whereas the processes involved from melanin synthesis in melanocytes to the transfer of melanosomes to keratinocytes are common among humans. Apart from the activities in the melanogenic rate-limiting enzyme, tyrosinase, in melanocytes and the amounts and distribution patterns of melanosomes in keratinocytes, the abilities of the actin-associated factors in charge of melanosome transport within melanocytes also regulate pigmentation. Mutations in genes encoding melanosome transport-related molecules, such as MYO5A, RAB27A and SLAC-2A, have been reported to cause a human pigmentary disease known as Griscelli syndrome, which is associated with diluted skin and hair color. Thus we hypothesized that process might play a role in modulating skin color variations. To address that hypothesis, the correlations of expression of RAB27A and its specific effector, SLAC2-A, to melanogenic ability were evaluated in comparison with tyrosinase, using human melanocytes derived from 19 individuals of varying skin types. Following the finding of the highest correlation in RAB27A expression to the melanogenic ability, darkly-pigmented melanocytes with significantly higher RAB27A expression were found to transfer significantly more melanosomes to keratinocytes than lightly-pigmented melanocytes in co-culture and in human skin substitutes (HSSs) in vivo, resulting in darker skin color in concert with the difference observed in African-descent and Caucasian skins. Additionally, RAB27A knockdown by a lentivirus-derived shRNA in melanocytes concomitantly demonstrated a significantly reduced number of transferred melanosomes to keratinocytes in co-culture and a significantly diminished epidermal melanin content skin color intensity (ΔL* = 4.4) in the HSSs. These data reveal the intrinsically essential role of RAB27A in human ethnic skin color determination and provide new insights for the fundamental understanding of regulatory mechanisms underlying skin pigmentation. 相似文献
7.
8.
Bondanza S Maurelli R Paterna P Migliore E Giacomo FD Primavera G Paionni E Dellambra E Guerra L 《Pigment cell research / sponsored by the European Society for Pigment Cell Research and the International Pigment Cell Society》2007,20(4):288-300
Vitiligo depigmentation is considered a consequence of either melanocyte disappearance or loss of functioning melanocytes in the involved areas. However, it has been reported that keratinocytes in involved vitiligo skin are damaged too. Based on this evidence, we evaluated the in vitro behaviour, in life span cultures, of involved and uninvolved vitiligo keratinocytes and their expression of proliferation, differentiation and senescence markers. An additional purpose was to investigate whether vitiligo keratinocytes from depigmented skin are able to sustain survival and growth of normal melanocytes (when added in co-culture experiments), as normal human keratinocytes manage to do. Our results demonstrate that almost all involved vitiligo keratinocytes have a shorter life span in vitro than the uninvolved cells and all of them do not maintain melanocytes in culture in a physiological ratio. Modification of proliferation and senescence marker expression also occurs. Indeed, we detected low initial expression levels of the senescence marker p16 in involved vitiligo keratinocytes, despite their shorter in vitro life span, and increased expression of proliferating cell nuclear antigen and p53. This preliminary analysis of a small number of in vitro cultured vitiligo keratinocytes suggests an impaired senescence process in lesional vitiligo keratinocytes and attempts to regulate it. 相似文献
9.
10.
Melanosomes synthesized within melanocytes are transferred to keratinocytes through dendrites, resulting in a constant supply of melanin to the epidermis, and this process determines skin pigmentation. During screening for inhibitors of melanosome transfer, we found a novel reagent, centaureidin, that induces significant morphological changes in normal human epidermal melanocytes and inhibits melanocyte dendrite elongation, resulting in a reduction of melanosome transfer in an in vitro melanocyte-keratinocyte co-culture system. Since members of the Rho family of small GTP-binding proteins act as master regulators of dendrite formation, and activated Rho promotes dendrite retraction, we studied the effects of centaureidin on the small GTPases. In in vitro binding assay, centaureidin activated Rho and furthermore, a Rho inhibitor (C. botulinum C3 exoenzyme), a Rho kinase inhibitor (Y27632) and a small GTPase inhibitor (Toxin B) blocked dendrite retraction induced by centaureidin. These results suggest centaureidin could act via the Rho signaling pathway, and it may directly or indirectly activate Rho. Thus, centaureidin appears to inhibit dendrite outgrowth from melanocytes by activating Rho, resulting in the inhibition of melanosome transfer from melanocytes to keratinocytes. 相似文献
11.
Hirobe T Furuya R Hara E Horii I Tsunenaga M Ifuku O 《Pigment cell research / sponsored by the European Society for Pigment Cell Research and the International Pigment Cell Society》2004,17(3):230-240
Repeated exposure of ultraviolet radiation B (UVB) on the dorsal skin of hairless mice induces the development of pigmented spots long after its cessation. The proliferation and differentiation of epidermal melanocytes in UVB-induced pigmented spots are greatly increased, and those effects are regulated by keratinocytes rather than by melanocytes. However, it remains to be resolved what factor(s) derived from keratinocytes are involved in regulating the proliferation and differentiation of epidermal melanocytes. In this study, primary melanoblasts (c. 80%) and melanocytes (c. 20%) derived from epidermal cell suspensions of mouse skin were cultured in a basic fibroblast growth factor-free medium supplemented with granulocyte-macrophage colony-stimulating factor (GM-CSF). GM-CSF induced the proliferation and differentiation of melanocytes in those keratinocyte-depleted cultures. Moreover, an antibody to GM-CSF inhibited the proliferation of melanoblasts and melanocytes from epidermal cell suspensions derived from the pigmented spots of UV-irradiated mice, but not from control mice. Further, the GM-CSF antibody inhibited the proliferation and differentiation of melanocytes co-cultured with keratinocytes derived from UV-irradiated mice, but not from control mice. The quantity of GM-CSF secreted from keratinocytes derived from the pigmented spots of UV-irradiated mice was much greater than that secreted from keratinocytes derived from control mice. Moreover, immunohistochemistry revealed the expression of GM-CSF in keratinocytes derived from the pigmented spots of skin in UV-irradiated mice, but not from normal skin in control mice. These results suggest that GM-CSF is one of the keratinocyte-derived factors involved in regulating the proliferation and differentiation of mouse epidermal melanocytes from UVB-induced pigmented spots. 相似文献
12.
KAREN A. HOLBROOK ARTHUR M. VOGEL ROBERT A. UNDERWOOD CAROLYN A. FOSTER 《Pigment cell & melanoma research》1988,1(Z1):6-17
Melanocytes account for approximately 5–10% percent of the cells in adult epidermis. Unlike the ectodermally derived keratinocytes, they originate in the neural crest and migrate into the epidermis early in development. There has been an interest in melanocytes in developing human skin since the late 1800s, when concentrated pigmented cells were identified in the sacro-coccygeal skin of Japanese fetuses. This observation led to speculation and subsequent investigation about the racial nature of the melanocytes in this site (the Mongolian spot), the presence of melanocytes in fetuses of other races, the timing of appearance of these cells in both the dermis and epidermis, and their origin. The early investigators relied primarily on histochemical methods that stained either the premelanosome or the pigmented melanosome, or relied upon the activity of tyrosinase within the melanosome to effect the DOPA reaction. Studies by electron microscopy added further documentation to the presence of melanocytes in the skin by resolving the structure of the melanosome regardless of its state of pigmentation. All of these methods recognized, however, only differentiated melanocytes. The thorough investigations of melanocytes in the skin from a large number of black embryos and fetuses by Zimmerman and colleagues between 1948 and 1955 provided insight into the time of appearance of melanocytes in the dermis (10–11 weeks' menstrual age) and the epidermis (11–12 weeks) and revealed the density of these cells in both zones of the skin of several regions of the body. The precise localization of the melanocytes in the developing hair follicles was contributed by the studies of Mishima and Widlan (J Invest Dermatol 1966; 46:263–277). More recently, monoclonal antibodies have been developed that recognize common oncofetal or oncodifferentiation antigens on the surface or in the cytoplasm of melanoma cells and developing melanocytes (but not normal adult melanocytes). These antibodies recognize the cells irrespective of the presence or absence of melanosomes or their activity in the synthesis of pigment and therefore are valuable tools for re-examining the presence, density, and distribution patterns of melanocytes in developing human skin. Using one of these antibodies (HMB-45), it was found that dendritic melanocytes are present in the epidermis between 40 and 50 days estimated gestational age in a density comparable with that of newborn epidermis and are distributed in relatively non-random patterns. A number of questions about the influx of cells into the epidermis, potential reservoirs of melanoblasts retained within the dermis, division of epidermal melanocytes, and the interaction of melanocytes and keratinocytes during development remain unresolved. The tools now appear to be available, however, to begin to explore many of these questions. 相似文献
13.
The protease-activated receptor 2 regulates pigmentation via keratinocyte-melanocyte interactions 总被引:11,自引:0,他引:11
Seiberg M Paine C Sharlow E Andrade-Gordon P Costanzo M Eisinger M Shapiro SS 《Experimental cell research》2000,254(1):25-32
Close association exists between melanocytes, the pigment melanin-producing cells in the body, and their neighboring keratinocytes. Keratinocytes are the pigment recipients and skin pigmentation is the result of this interaction. While the chemical basis of melanin production (melanogenesis) is well documented, the molecular mechanism of melanosome transfer needs to be elucidated. We are now providing first evidence that the protease-activated receptor 2 (PAR-2) expressed on keratinocytes, but not on melanocytes, is involved in melanosome transfer and therefore may regulate pigmentation. Activation of PAR-2 with trypsin or with the peptide agonist SLIGRL induced pigmentation in both two- and three-dimensional cocultures of keratinocytes and melanocytes, but not in cocultures that were spatially separated, indicating the need for intimate cell-cell contact. Topical application of SLIGRL on human skin transplanted on SCID mice resulted in a visible skin darkening. Histological examination revealed increased deposits of melanin in the keratinocytes. Inhibition of PAR-2 activation by RWJ-50353, a serine protease inhibitor, resulted in depigmentation and changes in expression of melanogenic-specific genes. Keratinocyte-melanocyte contact was essential for this depigmenting effect. Topical application of this inhibitor induced lightening of the dark skin Yucatan swine, which was confirmed by histochemical analysis. The results presented here suggest a novel mechanism for the regulation of pigmentation, mediated by the activation or inhibition of the keratinocyte receptor PAR-2. 相似文献
14.
Timothy L. Scott Kazumasa Wakamatsu Shosuke Ito John A. D’Orazio 《In vitro cellular & developmental biology. Animal》2009,45(10):577-583
The melanocortin 1 receptor (MC1R) is a transmembrane Gs-coupled surface protein found on melanocytes that binds melanocyte-stimulating hormone and mediates activation of adenylyl
cyclase and generation of the second messenger cyclic AMP (cAMP). MC1R regulates growth and differentiation of melanocytes
and protects against carcinogenesis. Persons with loss-of-function polymorphisms of MC1R tend to be UV-sensitive (fair-skinned and with a poor tanning response) and are at high risk for melanoma. Mechanistic studies
of the role of MC1R in melanocytic UV responses, however, have been hindered in part because Mc1r-defective primary murine melanocytes have been difficult to culture in vitro. Until now, effective growth of murine melanocytes
has depended on cAMP stimulation with adenylyl cyclase-activating or phosphodiesterase-inhibiting agents. However, rescuing
cAMP in the setting of defective MC1R signaling would be expected to confound experiments directly testing MC1R function on
melanocytic UV responses. In this paper, we report a novel method of culturing primary murine melanocytes in the absence of
pharmacologic cAMP stimulation by incorporating conditioned supernatants containing stem cell factor derived from primary
keratinocytes. Importantly, this method seems to permit similar pigment expression by cultured melanocytes as that found in
the skin of their parental murine strains. This novel approach will allow mechanistic investigation into MC1R’s role in the
protection against UV-mediated carcinogenesis and determination of the role of melanin pigment subtypes on UV-mediated melanocyte
responses. 相似文献
15.
Smith-Thomas LC Moustafa M Dawson RA Wagner M Balafa C Haycock JW Krauss AH Woodward DF MacNeil S 《Pigment cell research / sponsored by the European Society for Pigment Cell Research and the International Pigment Cell Society》2001,14(4):298-309
The purpose of this study was to examine some of the factors that may be relevant to regulating pigmentation in the human eye, specifically whether choroidal and iridial melanocytes are sensitive to regulation by epithelial and stromal cells and alpha-melanocyte stimulating hormone (alpha-MSH). Human choroidal and iridial melanocytes were established in culture and co-cultured with epithelial cells and stromal cells derived both from skin and from eye in order to determine their influence on choroidal and iridial melanocyte dopa oxidase activity. In all cases, co-culture of melanocytes with either epithelial cells or fibroblasts led to an increase in dopa oxidase activity during 5 days of co-culture. The extent of the increase ranged from 60% (non-significant) to as much as 185% when both fibroblasts and keratinocytes were present. The optimal ratio of fibroblasts to melanocytes was 1:10 (for dermal fibroblasts) or 1:2 (for iridial fibroblasts) and 1:1 for all epithelial cells to melanocytes. Both choroidal (three out of three cultures) and iridial (two out of three cultures) melanocytes showed increases in dopa oxidase activity to alpha-MSH when cultured in Green's media but the same cells cultured in MCDB153 were unresponsive to alpha-MSH. These in vitro studies suggest that ocular melanocytes have the capacity to be influenced by adjacent epithelial and stromal cells with respect to pigmentation. 相似文献
16.
Tomohisa Hirobe Rikako Furuya Eijiro Hara Izumi Horii Makoto Tsunenaga Ohji Ifuku 《Pigment cell & melanoma research》2004,17(3):230-240
Repeated exposure of ultraviolet radiation B (UVB) on the dorsal skin of hairless mice induces the development of pigmented spots long after its cessation. The proliferation and differentiation of epidermal melanocytes in UVB‐induced pigmented spots are greatly increased, and those effects are regulated by keratinocytes rather than by melanocytes. However, it remains to be resolved what factor(s) derived from keratinocytes are involved in regulating the proliferation and differentiation of epidermal melanocytes. In this study, primary melanoblasts (c. 80%) and melanocytes (c. 20%) derived from epidermal cell suspensions of mouse skin were cultured in a basic fibroblast growth factor‐free medium supplemented with granulocyte‐macrophage colony‐stimulating factor (GM‐CSF). GM‐CSF induced the proliferation and differentiation of melanocytes in those keratinocyte‐depleted cultures. Moreover, an antibody to GM‐CSF inhibited the proliferation of melanoblasts and melanocytes from epidermal cell suspensions derived from the pigmented spots of UV‐irradiated mice, but not from control mice. Further, the GM‐CSF antibody inhibited the proliferation and differentiation of melanocytes co‐cultured with keratinocytes derived from UV‐irradiated mice, but not from control mice. The quantity of GM‐CSF secreted from keratinocytes derived from the pigmented spots of UV‐irradiated mice was much greater than that secreted from keratinocytes derived from control mice. Moreover, immunohistochemistry revealed the expression of GM‐CSF in keratinocytes derived from the pigmented spots of skin in UV‐irradiated mice, but not from normal skin in control mice. These results suggest that GM‐CSF is one of the keratinocyte‐derived factors involved in regulating the proliferation and differentiation of mouse epidermal melanocytes from UVB‐induced pigmented spots. 相似文献
17.
Interactions between melanocytes and neighboring cells in the skin (keratinocytes and fibroblasts) play important roles in regulating human skin color. We recently reported that neuregulin-1 (NRG1) is highly expressed in fibroblasts from Fitzpatrick type VI skin (the darkest) and at least in part determines the constitutive color of human skin. We have now characterized the bioactive motif of NRG1 that is involved in modulating melanin production in human melanocytes. We found that 8-mer motifs (PSRYLCKC and LCKCPNEF) increased melanin production but did not increase the proliferation of melanocytes; the minimum fragment that could elicit that effect was the tetrapeptide LCKC. This smaller bioactive peptide might have an advantage in clinical applications in which it modulates only pigmentation and does not stimulate melanocyte proliferation. 相似文献
18.
Transformation of murine melanocytes by basic fibroblast growth factor cDNA and oncogenes and selective suppression of the transformed phenotype in a reconstituted cutaneous environment 总被引:15,自引:0,他引:15
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《The Journal of cell biology》1989,109(6):3115-3128
Constitutive expression of basic fibroblast growth factor (bFGF), a common characteristic of metastatic melanomas, was reproduced in vitro by infection of normal murine melanocytes with a recombinant retrovirus carrying a cDNA for bFGF. Expression of bFGF in these cells conferred autonomous growth in culture and extinguished differentiated functions, such as the synthesis of melanin and formation of dendrites. Independence from exogenous bFGF and loss of differentiated functions in vitro were induced also by transformation of melanocytes with the oncogenes myc, Ela, ras, and neu, although bFGF was not expressed by the respective transformants. As shown in skin reconstitution experiments onto syngeneic mice and subcutaneous injections into nude mice, the various transformants differed in their behavior in vivo. The bFGF transformants did not form tumors. They reverted to having a normal, melanotic phenotype and restricted growth. Myc and Ela transformants grew as tumors in nude mice but not in syngeneic, immunocompetent animals. Ras-transformed melanocytes were always tumorigenic, whereas the formation of tumors by neu transformants was suppressed by the concomitant grafting of keratinocytes in reconstituted skin of syngeneic mice. These data show that melanocytes genetically manipulated to produce bFGF acquire properties in vitro similar to those of metastatic melanoma cells or those induced by various oncogenes but that constitutive production of bFGF by itself is insufficient to make melanocytes tumorigenic. The experiments also show that melanocytes transformed by the selected oncogenes respond differentially to various environments in vivo. 相似文献
19.
Melanocyte function and its control by melanocortin peptides. 总被引:32,自引:0,他引:32
Marina Tsatmali Janis Ancans Anthony J Thody 《The journal of histochemistry and cytochemistry》2002,50(2):125-133
Melanocytes are cells of neural crest origin. In the human epidermis, they form a close association with keratinocytes via their dendrites. Melanocytes are well known for their role in skin pigmentation, and their ability to produce and distribute melanin has been studied extensively. One of the factors that regulates melanocytes and skin pigmentation is the locally produced melanocortin peptide alpha-MSH. The effects of alpha-MSH on melanogenesis are mediated via the MC-1R and tyrosinase, the rate-limiting enzyme in the melanogenesis pathway. Binding of alpha-MSH to its receptor increases tyrosinase activity and eumelanin production, which accounts for the skin-darkening effect of alpha-MSH. Other alpha-MSH-related melanocortin peptides, such as ACTH1-17 and desacetylated alpha-MSH, are also agonists at the MC-1R and could regulate melanocyte function. Recent evidence shows that melanocytes have other functions in the skin in addition to their ability to produce melanin. They are able to secrete a wide range of signal molecules, including cytokines, POMC peptides, catecholamines, and NO in response to UV irradiation and other stimuli. Potential targets of these secretory products are keratinocytes, lymphocytes, fibroblasts, mast cells, and endothelial cells, all of which express receptors for these signal molecules. Melanocytes may therefore act as important local regulators of a range of skin cells. It has been shown that alpha-MSH regulates NO production from melanocytes, and it is possible that the melanocortins regulate the release of other signalling molecules from melanocytes. Therefore, the melanocortin signaling system is one of the important regulators of skin homeostasis. 相似文献
20.
BHANU IYENGAR 《Pigment cell & melanoma research》1998,11(2):110-113
Epidermal pigmentation and UV exposure are related to the incidence of skin tumors. There is a higher incidence of UV related skin tumors in populations with low pigment and in vitiligo patients, resulting from DNA damage. Normally DNA repair processes set in with the expression of PCNA in the keratinocyte. The present study was conducted on the marginal zone skin in vitiligo. Whole skin organ cultures irradiated with increasing doses of UV in the 280–400 nm range show that in the depigmented area there is no expression of PCNA by the keratinocytes. In comparison, the marginal zone keratinocytes show a dose related positivity in the presence of UV responsive melanocytes. These photoresponsive melanocytes show dendricity and cytoplasmic PCNA positivity. The melanocytes interact with keratinocytes by active melanosome transfer. From this study it is suggested that this involves transfer of PCNA as well. The present study indicates the differentiating keratinocytes in skin do not express PCNA but appear to be dependent on active UV responding melanocytes for DNA repair. This factor could play an important role in the occurrence of UV-related skin tumors. 相似文献