细胞因子在白癜风发病机制中的作用

白癜风由于表皮黑素细胞的功能丧失而引起.细胞因子通过自分泌或旁分泌的方式影响黑素细胞的生物学特性.多种细胞因子及黑素细胞表面存在的细胞因子受体在黑素细胞的生长,分化、增殖、凋亡及其黑素产生及转运过程中起重要作用.促黑素细胞激素、粒细胞一巨噬细胞集落刺激因子、干细胞因子、碱性成纤维细胞生长因子等促进黑素细胞的生长、分化、增殖,肿瘤坏死因子-α、白介素等抑制黑素细胞生长.     

Th17细胞与白癜风的发病机制

白癜风是一种常见的皮肤病,其原因是皮肤黑素细胞的缺失。黑素细胞缺失的确切机制尚不清楚,研究指出,细胞免疫在白癜风发病机制中起到重要作用。在某些特定细胞因子的作用下,CD4＋T细胞分化为Th17细胞,Th17细胞可参与多种疾病的发病。在白癜风发病过程中,Thl7细胞和树突细胞数量增多,功能活跃。Th17细胞除主要分泌IL-17外,还分泌IL-6、IL-21、IL-22和肿瘤坏死因子d等细胞因子,他们参与白癜风发病,导致黑素细胞生成减少、萎缩、消失,黑素生成减少,最终形成白癜风。     

黑素细胞黑皮素-1受体

黑素细胞黑皮素 - 1受体在黑素的生成和调控方面起重要的作用 ,黑皮素 - 1受体功能的改变和基因突变与色素性皮肤病和皮肤肿瘤密切相关。在人皮肤中 ,几乎所有类型细胞均表达黑皮素 - 1受体 ,这预示黑皮素 - 1受体在皮肤病的发生和治疗上都具有一定的作用。现就黑素细胞黑皮素 - 1受体的配体、功能及其基因突变与皮肤病关系的研究进展作一介绍     

黑素细胞黑皮素—1受体

黑素细胞黑皮素－1受体在黑素的生成和调控方面起重要的作用，黑皮素－1受体功能的改变和基因突变与色素性皮肤病和皮肤肿瘤密切相关。在人皮肤中，几科所有类型细胞均表达黑皮素－1受体，这预示黑皮素－1受体在皮肤病的发生和治疗上都具有一定的作用。现就黑素细胞黑皮素－1受体的配体、功能及其基因突变与皮肤病关系的研究进展作一介绍。     

中药对黑素细胞生物学活性影响的研究进展

黑素细胞的数量及其生物学活性是引起色素性皮肤病的主要原因,传统中医中药治疗白癜风已在临床取得较好疗效,众多学者用不同的细胞株系及不同的研究方法观察了中药(包括单味、复方、单体)对黑素细胞酪氨酸酶活性、黑素细胞增殖和黑素生成的影响。初步阐述了中药治疗白癜风的有效机制。     

细胞因子对黑素细胞生物学特性的影响

多种细胞因子具有改变黑素细胞的形态、抑制其增殖及黑素合成,并对黑素细胞表达细胞间粘连分子、HLA-Ⅱ类抗原、黑素瘤相关抗原,以及分泌纤维联结蛋白产生影响作了介绍。阐述了在皮肤色素减退过程中细胞因子所起的作用。     

黑素细胞的生物学和黑素生成的新进展

近年来 ,已有少数新药用于治疗色素性皮肤病 ,已列出药理学干预黑素细胞和黑素生成的一些靶位。弄清皮肤生理性自然光防护、黑素细胞和黑素作用以及黑素生成的调控机理 ,以便采取新的安全措施来纠正异常肤色 ,增强皮肤预防长期过度日晒后的有害作用     

白癜风皮损中非黑素细胞进展

白癜风的发病机制尚未完全明了.其发病除黑素细胞异常外,还涉及非黑素细胞的变化,近年来非黑素细胞在白癜风中的研究逐渐增多.研究表明,一些皮肤非黑素细胞如角质形成细胞、朗格汉斯细胞、成纤维细胞等与黑素细胞关系密切,这些细胞影响黑素细胞的迁移、增殖、分化等功能.白癜风皮损中非黑素细胞超微结构的异常和分泌细胞因子的变化可影响黑素细胞的活性及凋亡,影响皮肤色素生成,从而参与白癜风发病.     

黑素细胞的生物学和黑素生成的新进展

近年来，已有少数新药用于治疗色素性皮肤病，已列出药理学干预黑素细胞和黑素生成的一些靶位。弄清皮肤生理性自然光防护、黑素细胞和黑素作用以及黑素生成的调控机理，以便采取新的 安全措施来纠正异常肤色，增强皮肤预防长期过度日晒后的有害作用。     

瞬时受体电位通道在黑素细胞中的作用及相关疾病研究

【摘要】 瞬时受体电位通道（TRP通道）是位于细胞膜或细胞器膜上的一种特殊类型的非选择性阳离子通道家族，在黑素细胞中显著表达。本文综述近年来TRP通道在黑素细胞中的生理功能及其参与色素性皮肤病及黑素瘤病理过程的相关研究进展，为黑素相关疾病的防治提供新的理论基础。     

Pigmented eccrine poromas: expression of melanocyte-stimulating cytokines by tumour cells does not always result in melanocyte colonization

Background Although eccrine poroma (EP) occurs preferentially in palmoplantar areas, pigmented variants of EP have not been documented on the palms and soles. Objectives We seek to confirm the notion regarding lack of pigmented EP on palmoplantar areas and determine whether the absence of pigmentation in palmoplantar EPs is due to lack of expression of melanocyte‐stimulating cytokines by tumour cells. Methods We searched the PubMed and Web of Science databases (1966–2006) for reports of pigmented EPs. In addition, a total of 17 EPs were collected from our pathology department. The presence of melanin was examined with haematoxylin‐eosin sections, and melanocyte colonization was shown by immunohistochemical stains for tyrosinase. In addition, immunohistochemical staining with antibodies to melanocyte‐stimulating cytokines, including endothelin‐1, stem cell factor, and nerve growth factor, was done on these tumours. Results A review of the literature revealed 15 pigmented EP reports, none of which were located in palmoplantar areas. Among 17 EPs collected from our pathology department, 7 occurred in palmoplantar areas and 10 in non‐palmoplantar areas. Three of the palmoplantar EPs and three of the non‐palmoplantar EPs showed positive staining with melanocyte‐stimulating cytokines. However, none of the palmoplantar EPs contained melanocytes or melanin pigment, wheras the three non‐palmoplantar EPs that stained positively with melanocyte‐stimulating cytokines were colonized with melanocytes and showed pigmentation clinically. Conclusions The expression of melanocyte‐stimulating factors by tumour cells is associated with melanocyte colonization in non‐palmoplantar EPs but not palmoplantar EPs. Therefore, the presence of melanocyte‐stimulating cytokines per se is not sufficient by itself to induce melanocyte colonization. Certain characteristics of palmoplantar skin, such as the dermal components of these anatomical sites, may play a role in inhibiting melanocyte colonization of EPs.     

RXRα ablation in epidermal keratinocytes enhances UVR-induced DNA damage, apoptosis, and proliferation of keratinocytes and melanocytes

We show here that keratinocytic nuclear receptor retinoid X receptor-α (RXRα) regulates mouse keratinocyte and melanocyte homeostasis following acute UVR. Keratinocytic RXRα has a protective role in UVR-induced keratinocyte and melanocyte proliferation/differentiation, oxidative stress-mediated DNA damage, and cellular apoptosis. We discovered that keratinocytic RXRα, in a cell-autonomous manner, regulates mitogenic growth responses in skin epidermis through secretion of heparin-binding EGF-like growth factor, GM-CSF, IL-1α, and cyclooxygenase-2 and activation of mitogen-activated protein kinase pathways. We identified altered expression of several keratinocyte-derived mitogenic paracrine growth factors such as endothelin 1, hepatocyte growth factor, α-melanocyte stimulating hormone, stem cell factor, and fibroblast growth factor-2 in skin of mice lacking RXRα in epidermal keratinocytes (RXRα(ep-/-) mice), which in a non-cell-autonomous manner modulated melanocyte proliferation and activation after UVR. RXRα(ep-/-) mice represent a unique animal model in which UVR induces melanocyte proliferation/activation in both epidermis and dermis. Considered together, the results of our study suggest that RXR antagonists, together with inhibitors of cell proliferation, can be effective in preventing solar UVR-induced photocarcinogenesis.     

Narrow-band ultraviolet-B stimulates proliferation and migration of cultured melanocytes

Narrow-band ultraviolet-B (UVB) radiation is an effective treatment for vitiligo vulgaris. However, the mechanisms of narrow-band UVB in inducing repigmentation of vitiligo lesions are not thoroughly clarified. The purpose of our study was to investigate the effects of narrow-band UVB irradiation on melanocyte proliferation and migration in vitro. Our results showed that the cell counts as well as [3H]thymidine uptake of melanocytes were significantly enhanced by narrow-band UVB-irradiated keratinocyte supernatants. In these supernatants, a significant increase in basic fibroblast growth factor (bFGF) and in endothelin-1 (ET-1) release was observed. bFGF is a natural mitogen for melanocytes, whereas ET-1 can stimulate DNA synthesis in melanocytes. This stimulatory effect of melanocyte proliferation by supernatants derived from narrow-band UVB-irradiated keratinocytes was significantly reduced by a selective endothelin-B (ET-B) receptor antagonist (BQ788), suggesting an essential role of ET-1 on melanocyte proliferation. Our results of time-lapse microphotography revealed a stimulatory effect of narrow-band UVB irradiation on melanocyte migration. Focal adhesion kinase (FAK) plays a pivotal role in cell migration. Phosphorylated FAK (p125(FAK)) expression on melanocyte was enhanced by narrow-band UVB irradiation. In this study, narrow-band UVB irradiation stimulated a significant increase in matrix metalloproteinase-2 (MMP-2) activity in melanocyte supernatants. Narrow-band UVB-irradiation-induced migration of melanocytes was significantly annihilated by the addition of p125(FAK) inhibitor (herbimycin-A) or MMP-2 inhibitor (GM6001). These results suggest that p125(FAK) and MMP-2 activity play important roles in narrow-band UVB-induced migration of melanocytes. Our results provide a theoretical basis for the effectiveness of narrow-band UVB irradiation in treating vitiligo.     

Helium-neon laser irradiation stimulates migration and proliferation in melanocytes and induces repigmentation in segmental-type vitiligo

Low-energy helium-neon lasers (632.8 nm) have been employed in a variety of clinical treatments including vitiligo management. Light-mediated reaction to low-energy laser irradiation is referred to as biostimulation rather than a thermal effect. This study sought to determine the theoretical basis and clinical evidence for the effectiveness of helium-neon lasers in treating vitiligo. Cultured keratinocytes and fibroblasts were irradiated with 0.5-1.5 J per cm2 helium-neon laser radiation. The effects of the helium-neon laser on melanocyte growth and proliferation were investigated. The results of this in vitro study revealed a significant increase in basic fibroblast growth factor release from both keratinocytes and fibroblasts and a significant increase in nerve growth factor release from keratinocytes. Medium from helium-neon laser irradiated keratinocytes stimulated [3H]thymidine uptake and proliferation of cultured melanocytes. Furthermore, melanocyte migration was enhanced either directly by helium-neon laser irradiation or indirectly by the medium derived from helium-neon laser treated keratinocytes. Thirty patients with segmental-type vitiligo on the head and/or neck were enrolled in this study. Helium-neon laser light was administered locally at 3.0 J per cm2 with point stimulation once or twice weekly. The percentage of repigmented area was used for clinical evaluation of effectiveness. After an average of 16 treatment sessions, initial repigmentation was noticed. Marked repigmentation (>50%) was observed in 60% of patients with successive treatments. Basic fibroblast growth factor is a putative melanocyte growth factor, whereas nerve growth factor is a paracrine factor for melanocyte survival in the skin. Both nerve growth factor and basic fibroblast growth factor stimulate melanocyte migration. It is reasonable to propose that helium-neon laser irradiation clearly stimulates melanocyte migration and proliferation and mitogen release for melanocyte growth and may also rescue damaged melanocytes, therefore providing a microenvironment for inducing repigmentation in vitiligo.     

Sema4D, the ligand for Plexin B1, suppresses c-Met activation and migration and promotes melanocyte survival and growth

Semaphorins are secreted and membrane-bound proteins involved in neural pathfinding, organogenesis, and tumor progression, through Plexin and neuropilin receptors. We recently reported that Plexin B1, the Semaphorin 4D (Sema4D) receptor, is a tumor-suppressor protein for melanoma, which functions, in part, through inhibition of the oncogenic c-Met tyrosine kinase receptor. In this report, we show that Sema4D is a protective paracrine factor for normal human melanocyte survival in response to UV irradiation, and that it stimulates proliferation and regulates the activity of the c-Met receptor. c-Met receptor signaling stimulates melanocyte migration, partly through downregulation of the cell adhesion molecule E-cadherin. Sema4D suppressed activation of c-Met in response to its ligand, hepatocyte growth factor (HGF), and partially blocked the suppressive effects of HGF on E-cadherin expression in melanocytes and HGF-dependent migration. These data demonstrate a role for Plexin B1 in maintenance of melanocyte survival and proliferation in the skin, and suggest that Sema4D and Plexin B1 act cooperatively with HGF and c-Met to regulate c-Met-dependent effects in human melanocytes. Because our data show that Plexin B1 is profoundly downregulated by UVB in melanocytes, loss of Plexin B1 may accentuate HGF-dependent effects on melanocytes, including melanocyte migration.     

Regulation of human melanocyte growth, dendricity, and melanization by keratinocyte derived factors

Epidermal pigmentation involves the synthesis of melanin in melanocytes and its transfer to surrounding keratinocytes, where it functions in photoprotection. To investigate the possible role of the keratinocyte in regulating pigmentation, human keratinocytes were incubated for 24 h in a defined culture medium, which was then transferred to pure human melanocyte cultures. After 1 week, the conditioned medium produced a fourfold increase in melanocyte yield and a seven-fold increase in total melanin. Increased melanocyte dendricity was clearly visible within 24 h as well. Ultrafiltration of the keratinocyte-conditioned medium suggested approximately one-half of the growth promoting activity as well as most of the dendricity and melanization stimulating activities were of low molecular weight (less than 500 Da). High molecular weight fractions stimulated only melanocyte growth. Of the several known keratinocyte-derived factors tested, none could be implicated as a mediator of the observed effects. Basic fibroblast growth factor, known to stimulate melanocyte growth in some culture systems, failed to stimulate growth, dendricity, or melanin content when added to the complete non-conditioned medium. Interleukin-1 alpha, interleukin-1 beta, 12-hydroxyeicosatetraenoic acid, prostaglandin E2, leukotriene B4, and adenosine 3',5'-cyclic monophosphate analogues also had no effect. These studies demonstrate that keratinocytes in vitro release factors that modulate melanocyte behavior and expand our understanding of controls for human epidermal pigmentation.     

Increased basic fibroblast growth factor levels in serum and blister fluid from patients with vitiligo

Basic fibroblast growth factor (bFGF) is a pleiotropic growth factor which has a high capacity for stimulating normal melanocyte proliferation and suppressing melanogenesis. The close and complicated relationship between bFGF, melanocyte proliferation and melanogenesis raises the theoretical possibility that bFGF may also be involved in the pathomechanism leading to vitiligo. The aim of this study was to compare the serum and suction blister fluid bFGF levels of vitiligo patients (9 females, 11 males) with those of healthy controls (3 females, 8 males). Vitiliginous skin-blister fluid bFGF levels and serum levels were significantly higher in vitiligo patients compared with healthy normal controls. Our data indicate that bFGF might be involved in the pathogenetic chain of events leading to vitiligo. Further studies are needed to define the exact role of bFGF and various other melanocytic mitogens in this disease.