Histamine is involved in ultraviolet B-induced pigmentation of guinea pig skin. (65/783)

We previously reported that histamine induced melanogenesis in cultured human melanocytes and that the stimulatory effect was mediated by protein kinase A activation via H2 receptors. It is well-known that ultraviolet B irradiation causes acute inflammation, known as erythema, and subsequent pigmentation, and there are several reports demonstrating an elevation of the histamine levels in ultraviolet B-irradiated skin. Thus, to evaluate the involvement of histamine in ultraviolet B-induced skin pigmentation, we examined the effect of an H2 antagonist in brownish guinea pig skin. Daily exposure to 200 mJ per cm2 ultraviolet B for 3 d evoked erythema and subsequent pigmentation in the skin samples tested. Moreover, a remarkable increase in dopa-positive melanocytes was observed in the pigmented area, which showed an increase in melanin synthesis. Topical application of famotidine, an H2 antagonist, significantly reduced pigmentation and moderated the increase of dopa-positive melanocytes in the ultraviolet B-irradiated skin. Even when the initiation of famotidine application was delayed to day 2 after irradiation, an inhibitory activity on ultraviolet B-induced pigmentation was observed; however, the ultraviolet B-induced erythema was not suppressed by topically applied famotidine. Thus, we concluded that histamine is involved in ultraviolet B-induced pigmentation and that famotidine suppressed the pigmentation by the prevention of histamine binding to H2 receptors in melanocytes but not by prevention of ultraviolet B permeability and inflammation.  (+info)

Donor specific response of estrogen and progesterone on cultured human melanocytes. (66/783)

The mechanisms of estrogen and progesterone in human cutaneous pigmentation are largely unknown. The molecular identification of estrogen receptor (ER) and progesterone receptor (PR) in the human melanocytes is of great importance to understand the mechanisms. We performed immunocytochemistry analysis and demonstrated that ER and PR were expressed in the cytoplasms and nuclei of human melanocytes. Reverse transcriptase-polymerase chain reaction (RT-PCR) and sequence analysis confirmed the expression of ER and PR at the transcriptional level. Despite of the presence of ER and PR, the physiological and pregnant levels of estrogen and progesterone showed inconsistent effects on the proliferation and tyrosinase activity of cultured human melanocytes. These results suggest that human melanocytes express ER and PR, which have a donor-specific action in human pigmentation. Further studies are needed to elucidate the induction mechanism and functions of these receptors, and the role of estrogen and progesterone in melanocytes.  (+info)

Evolution of melanocytic nevi on the faces and necks of adolescents: a 4 y longitudinal study. (67/783)

All melanocytic nevi on the faces and necks of a cohort of students, initially aged 12-14 y, were mapped and photographed annually for 4 y. The features of each nevus were charted yearly noting changes in size and profile, and the appearance or disappearance of any nevi on a student's face and neck was recorded. Nevi were classified by size (small, < 2 mm; medium, 2-5 mm; large, > 5 mm), and by profile (flat, raised). Data from 20 adolescents selected randomly from the cohort for detailed analysis showed males had about twice as many nevi as females, but there was little difference between sexes in their patterns of nevus development. Approximately half the nevi were small in all years; under 5% were large. Over the 4 y of follow-up the proportion of flat nevi dropped from 70% to 57%, whereas nevus numbers increased by 47% in year 1, with smaller increases in older students. Most new or disappearing nevi were small and flat, although both incident and disappearing nevi could be larger and/or raised. Of the existing nevi that altered in the follow-up period, the tendency was towards an increase in size among raised but not among flat nevi; a lowering of profile among small nevi; and a raising of profile among larger nevi; but there were many exceptions to this pattern. Among several host factors examined, inability to tan after sun exposure was found to be significantly negatively associated with the propensity of nevi to change size over the study period. Overall our findings indicate that, contrary to conventional belief, there is a measurable turnover among melanocytic nevi even in early life.  (+info)

Dietary carotenoids contribute to normal human skin color and UV photosensitivity. (68/783)

The aim of the current study was to determine whether dietary carotenoids influence skin pigmentation and UV photosensitivity in a healthy unsupplemented panel (n = 22) of Caucasian (skin Type II) subjects. Skin spectrophotometric and tristimulus (L*a*b*) CR200 chromameter readings were made at various body sites to objectively measure skin carotenoid levels and skin color, respectively. The minimal erythemal dose (MED) was also measured to determine the intrinsic UV photosensitivity of the skin. We found that tristimulus b* values (but not L* and a* values) were consistently and closely correlated with skin carotenoid levels at a number of body sites including the back (r = 0.85, P < 0.00001), forehead (r = 0.85, P < 0.00001), inner forearm (r = 0.75, P < 0.0001) and palm of the hand (r = 0.78, P < 0.0001). Skin carotenoid levels and MED were also correlated in these subjects (r = 0.66, P < 0.001), as were tristimulus b* values and MED (r = 0.71, P < 0.0002). From these observations, we conclude that carotenoids from a normal, unsupplemented diet accumulate in the skin and confer a measurable photoprotective benefit (at least in lightly pigmented Caucasian skin), that is directly linked to their concentration in the tissue. Carotenoids also appear to contribute measurably and significantly to normal human skin color, in particular the appearance of "yellowness" as defined objectively by CR200 tristimulus b* values. On the basis of these findings we believe that objective measurements of skin color, in particular tristimulus b* values, may be a potentially useful means of monitoring dietary carotenoid status and assessing UV photosensitivity in Caucasian populations.  (+info)

Protease-activated receptor 2, a receptor involved in melanosome transfer, is upregulated in human skin by ultraviolet irradiation. (69/783)

Previous studies have shown that the protease-activated receptor 2 is involved in skin pigmentation through increased phagocytosis of melanosomes by keratinocytes. Ultraviolet irradiation is a potent stimulus for melanosome transfer. We show that protease-activated receptor 2 expression in human skin is upregulated by ultraviolet irradiation. Subjects with skin type I, II, or III were exposed to two or three minimal erythema doses of irradiation from a solar simulator. Biopsies were taken from nonexposed and irradiated skin 24 and 96 h after irradiation and protease-activated receptor 2 expression was detected using immunohistochemical staining. In nonirradiated skin, protease-activated receptor 2 expression was confined to keratinocytes in the lower one-third of the epidermis. After ultraviolet irradiation protease-activated receptor 2 expression was observed in keratinocytes in the upper two-thirds of the epidermis or the entire epidermis at both time points studied. Subjects with skin type I showed delayed upregulation of protease-activated receptor 2 expression, however, compared with subjects with skin types II and III. Irradiated cultured human keratinocytes showed upregulation in protease-activated receptor 2 expression as determined by immunofluorescence microscopy and Western blotting. Cell culture supernatants from irradiated keratinocytes also exhibited a dose-dependent increase in protease-activated receptor-2 cleavage activity. These results suggest an important role for protease-activated receptor-2 in pigmentation in vivo. Differences in protease-activated receptor 2 regulation in type I skin compared with skin types II and III suggest a potential mechanism for differences in tanning in subjects with different skin types.  (+info)

Skin melanin, hemoglobin, and light scattering properties can be quantitatively assessed in vivo using diffuse reflectance spectroscopy. (70/783)

Noninvasive and real-time analysis of skin properties is useful in a wide variety of applications. In particular, the quantitative assessment of skin in terms of hemoglobin and melanin content, as well as in terms of its light scattering properties, is a challenging problem in dermatology. We present here a technique for examining human skin, based on the in vivo measurement of diffuse reflectance spectra in the visible and near-infrared ranges of the electromagnetic spectrum. Spectra were measured by means of a fiber optic probe, and they were analyzed using an analytical model of light diffusion in the skin. The results of the analysis indicate that it is possible to obtain quantitative information about hemoglobin and melanin content, as well as basic information regarding the scattering properties of the skin.  (+info)

Direct evidence to support the role of antigen-specific CD8(+) T cells in melanoma-associated vitiligo. (71/783)

Vitiligo is a cutaneous pigmentary disorder characterized by the loss of melanocytes. An autoimmune mechanism is strongly suspected to be involved in this affection given that it is frequently associated with autoimmune hormonal disorders, and because antibodies directed against melanocytic antigens are found in the serum of patients with vitiligo. We examined the role of cellular immunity in melanoma-associated vitiligo by expanding infiltrating lymphocytes from fresh biopsy specimens of vitiligo patches in melanoma patients. The vitiligo-infiltrating lymphocytes were almost exclusively T lymphocytes, and most were CD8(+). Following in vitro expansion, vitiligo-infiltrating lymphocytes remained predominantly CD8(+) and expressed the cutaneous homing receptor CLA. Furthermore, vitiligo-infiltrating lymphocytes had a clonal or oligoclonal T cell receptor profile, possibly reflecting specific antigenic stimulation. Finally, vitiligo- infiltrating lymphocytes specifically recognized differentiation antigens shared by normal melanocytes and melanoma cells. This direct demonstration of CD8(+) T cell involvement in vitiligo suggests that, in melanoma patients, vitiligo may be a visible effect of a spontaneous antitumoral immune response.  (+info)

(4-Methoxy-benzylidene)-(3-methoxy-phenyl)-amine, a nitrogen analog of stilbene as a potent inhibitor of melanin production. (72/783)

The current study was carried out to investigate in vitro the effects of (4-methoxy-benzylidene)-(3-methoxyphenyl)-amine on melanin biosynthesis which is closely related to hyper-pigmentation. (4-Methoxy-benzylidene)-(3-methoxy-phenyl)-amine, a nitrogen analog of stilbene, was synthesized by a single step process. This compound inhibited the tyrosinase activity, which converts dopa to dopachrome in the biosynthetic process of melanin, and showed a UV-blocking effect at UV-B band. The compound also exhibited SOD-like activity, which is involved in the protection against auto-oxidation and inhibited melanin production in melan-a cell line. Our results suggest the possibility that (4-methoxy-benzylidene)-(3-methoxy-phenyl)-amine might be used as a skin whitening agent.  (+info)