endothelin-1 and Vitiligo

To observe the therapeutic effect of Xiaobai Mixture (XBM) in treating vitiligo.. Seventy-four patients with vitiligo were randomly divided into the XBM group treated with XBM and the control group treated with 8-MOP. The therapeutic effect, nail-fold microcirculation, plasma endothelin-1, serum immunoglobulin were observed and compared.. The therapeutic effect of XBM was better than that of 8-MOP (P < 0.05). XBM could also obviously improve the nail-fold microcirculation, elevate the plasma endothelin-1 level and lower the serum IgG (P < 0.01).. XBM has superiority in treating vitiligo.

Topics: Adolescent; Adult; Drugs, Chinese Herbal; Endothelin-1; Female; Humans; Immunoglobulin G; Male; Microcirculation; Middle Aged; Nails; Phytotherapy; Vitiligo

Endothelin-1 (ET-1), expressed by keratinocytes, has paracrine effects on melanocytes. The endothelin 1-axis [ET-1, endothelin A receptor (ETAR) and endothelin B receptor (ETBR)] is thought to play a role in the depigmentation process occurring in vitiligo, with no studies on the cutaneous protein expression of this axis in the disease. The aim of the present study was to compare the expression of ET-1 axis in lesional and perilesional normal epidermis of vitiligo patients with healthy controls. Ten patients with non-segmental stable vitiligo and ten healthy controls were included. Skin biopsies from all subjects were studied immunohistochemically for ET-1, ETAR and ETBR expression. No significant difference was detected in the rate of expression and the degree of staining of ET-1 axis in controls compared with each of lesional vitiligo and perilesional normal epidermis (P>0.05). There was no statistically significant difference between lesional vitiligo and perilesional normal epidermis regarding to the rates of ET-1, ETAR and ETBR expression (P=0.82, P=0.5 and P=0.99, respectively). Semi-quantitative analysis of ETAR revealed higher staining grades in lesional compared with perilesional normal epidermis, with a statistically significant difference (P=0.04). There was no statistically significant difference between the two groups regarding the staining grades of ET-1 and ETBR (P>0.05 for both markers). A highly significant positive correlation was found between ET-1 and ETAR (r =0.99, P<0.05) and between ET-1 and ETBR (r=0.87, P<0.05). The study demonstrated unaltered expression of ET-1 axis in keratinocytes in lesional vitiligo and perilesional normal epidermis. Additional studies on the differential expression of this axis in keratinocytes and melanocytes are therefore required.

Topics: Adult; Endothelin-1; Epidermis; Female; Humans; Immunohistochemistry; Keratinocytes; Male; Melanocytes; Pilot Projects; Receptor, Endothelin A; Receptor, Endothelin B; Vitiligo; Young Adult

Topics: Adult; Endothelin-1; Female; Fibroblast Growth Factor 2; Humans; Keratinocytes; Male; Middle Aged; RNA, Messenger; Skin Pigmentation; Skin Transplantation; Stem Cell Factor; Ultraviolet Rays; Ultraviolet Therapy; Vitiligo

Vitiligo is an acquired pigmentary disorder caused by the destruction of melanocytes. Two of the major theories regarding the pathogenesis of vitiligo are the autoimmune theory and autocytotoxicity theory, but, the precise pathogenetic mechanism is still not clarified.. We investigated the effects of ET-1, tacrolimus and tumour necrosis factor-α (TNF-α) on proliferation and migration of cultured normal human melanocytes (NHMs). We also sought to clarify the theoretical rationale underlying the topical tacrolimus monotherapy or tacrolimus-UV combination therapy as tools for vitiligo treatment.. The effects of ET-1, tacrolimus and TNF-α on proliferation/migration of cultured NHMs were investigated by MTT assay/Boyden chamber transwell migration assay. We also examined roles of CXC-chemokine receptor II (CXCR II) and matrix metalloproteinases (MMPs) in such conditions.. ET-1 exerted a stimulatory effect on melanocyte proliferation and migration, but, tacrolimus exerted a stimulatory effect only on melanocyte migration higher than ET-1. TNF-α inhibited melanocyte proliferation in a dose-dependent manner. Paradoxically, TNF-α-pretreated NHMs exhibited an enhanced proliferative efficiency after being switched to ET-1. We found CXCRII was highly expressed in TNF-α-incubated melanocytes than the agents-free control, and ET-1 treatment after TNF-α preincubation showed the higher levels of CXCRII expression than the condition incubated with TNF-α alone. Moreover, the greater activities of MMP-2 and MMP-9 induced by tacrolimus than ET-1, reflected tacrolimus would enhance migration stimulatory effect in cultured NHMs.. Topical tacrolimus can be used an effective agent for vitiligo treatment as monotherapy, maybe due to its migration stimulatory action or TNF-α inhibitory property, and also as a component in combination therapy with UV treatment, considering the more upregulated MMPs activities are induced and the more effective migrations are feasible by itself than ET-1.

Topics: Cell Movement; Cell Proliferation; Endothelin-1; Humans; Immunosuppressive Agents; Matrix Metalloproteinase 2; Matrix Metalloproteinase 9; Melanocytes; Phototherapy; Receptors, CXCR; Tacrolimus; Tumor Necrosis Factor-alpha; Vitiligo

Vitiligo vulgaris is a depigmentary disorder resulting from the disappearance of functional melanocytes. Currently, the pathogenesis of this disorder remains obscure.. Genetic analysis of patients with vitilgo may provide important clues for elucidating the complex pathomechanisms involved in the disease process. Because dysfunctional keratinocytes have recently been implicated in the pathogenesis of vitiligo vulgaris, we conducted a case-control association study to investigate this phenomenon.. Fifty-one patients with vitiligo vulgaris and 118 healthy controls from Taiwan were recruited to investigate the association between relevant keratinocyte-related genes and the occurrence of vitiligo vulgaris. This study genotyped 11 single-nucleotide polymorphisms (SNPs) in five genes including stem cell factor (SCF, also known as KITLG), basic fibroblast growth factor (bFGF, also known as NuDT6), endothelin-1 (EDN1), hepatocyte growth factor (HGF) and stem cell growth factor (SCGF, also known as CLEC11A).. Our results revealed that the A allele for SNP rs11104947 in the SCF gene and the T allele for SNP rs13866 in the SCGF gene were, respectively, associated with a 1.95- and a 2.14-fold risk of developing vitiligo vulgaris. A higher risk was also detected among subjects who carried the SCF rs995029/rs11104947 C/A haplotype (odds ratio = 2.45). Furthermore, the at-risk alleles for SCF rs11104947 (A allele) and for SCGF SNP rs13866 (T allele) were found to display a 7.92-fold increased gene-gene combined risk. No significant relationship between polymorphic frequency for genes bFGF, EDN1 as well as HGF and occurrence of vitiligo vulgaris was observed.. These novel genetic findings provide new insights in relation to the mechanisms that might be involved in the development of vitiligo vulgaris.

Topics: Adult; Asian People; Case-Control Studies; Endothelin-1; Female; Fibroblast Growth Factor 2; Genetic Predisposition to Disease; Hematopoietic Cell Growth Factors; Hepatocyte Growth Factor; Humans; Keratinocytes; Lectins, C-Type; Male; Middle Aged; Polymorphism, Single Nucleotide; Stem Cell Factor; Taiwan; Vitiligo; Young Adult

Vitiligo is a skin disorder affected by genetic, environmental, local and endocrine factors. Endothelin-1, which is expressed by keratinocytes, has paracrine effects on melanocytes, influencing their homeostasis, proliferation and pigmentation. It is thought to play a role in the skin response to 311-nm, narrow-band ultraviolet irradiation.. To investigate the association of endothelin-1 gene (EDN1) polymorphisms with vitiligo in a Korean population.. To evaluate the expression of endothelin-1 in cultured human keratinocytes after irradiation with narrow-band ultraviolet B (NBUVB), we performed RT-PCR and ELISA. In addition, we genotyped 312 vitiligo patients and 313 matched-healthy controls, and compared the genotype, allele and haplotype frequencies of EDN1 polymorphisms (intron 4 G/A, rs2071942 and exon 5 G/T, rs5370) between the two groups, using PCR-restriction fragment length polymorphism. The effects of sex, onset age, the presence of autoimmune diseases, family history and clinical type were analysed statistically.. NBUVB induced the expression of endothelin-1 in cultured human keratinocytes. The genotype distributions and allele frequencies of EDN1 polymorphisms did not differ significantly between vitiligo patients and healthy controls. Moreover, the results were not related to sex, onset age, the presence of autoimmune diseases or family history. Interestingly, the haplotype frequencies of EDN1 polymorphisms differed significantly between vitiligo patients and healthy controls. When analysed according to clinical type, the haplotype frequencies in the focal and segmental clinical types differed significantly from healthy controls.. This study suggests that EDN1 is related to the development of vitiligo in the Korean population.

Topics: Adolescent; Adult; Case-Control Studies; Cells, Cultured; Endothelin-1; Enzyme-Linked Immunosorbent Assay; Female; Gene Frequency; Genetic Predisposition to Disease; Genotype; Humans; Infant, Newborn; Keratinocytes; Male; Middle Aged; Polymorphism, Single Nucleotide; Reverse Transcriptase Polymerase Chain Reaction; Risk Factors; Skin; Ultraviolet Rays; Vitiligo

Recent evidence suggests that systemic psoralen plus ultraviolet A (PUVA) therapy may have a stimulatory effect on melanocytes, not only locally but also systemically. Aim. We aimed to assess endothelin-1 (ET-1), a potent melanocyte mitogen, in plasma of PUVA-treated paients with vitiligo.. ET-1 was sequentially assessed (using ELISA) in patients with nonsegmental vitiligo treated with PUVA (n = 20), at 8, 16 and 24 h following the PUVA session. Evaluations took place at 0, 1 and 3 months of therapy. Patients with psoriasis (n = 15) treated identically and healthy subjects not receiving any therapy (n = 15) served as controls. Vitiligo Area Scoring Index (VASI) and Psoriasis Area Severity Index (PASI) scores were simultaneously evaluated.. ET-1 was significantly lower in vitiligo than in psoriasis at month 0 (8.2 +/- 3.6 vs. 13.7 +/- 5.4 pg/mL; P = 0.03) and it was significantly higher in both than in healthy controls at all time points of the PUVA sessions (P < 0.001). In vitiligo, it significantly increased at month 3 at 8 (8.2 +/- 3.6 vs. 10.8 +/- 2.7 pg/mL; P = 0.02) and 16 h (8.2 +/- 3.6 vs. 11.5 +/- 3.9 pg/mL; P < 0.01), whereas in psoriasis, it significantly decreased at month 3 at 8 (13.7 +/- 5.4 vs. 3.5 +/- 0.4 pg/mL; P < 0.01) and 16 h (13.7 +/- 5.4 vs. 6.3 +/- 4 pg/mL; P = 0.01). In contrast to psoriasis, sequential values of vitiligo revealed insignificant variance (P > 0.05). VASI score significantly decreased at month 3 (19 +/- 9.6 vs. 11.9 +/- 7.3; P < 0.01), whereas PASI score significantly decreased at months 1 (38.2 +/- 16.1 vs. 13.8 +/- 3; P < 0.05) and 3 (38.2 +/- 16.1 vs. 7 +/- 2.6; P = 0.03). There was a significant indirect correlation of ET-1 with VASI score (P < 0.01) and a significant direct correlation with PASI score (P < 0.01).. Systemic PUVA therapy in vitiligo may have a generalized mitogenic effect on melanocytes through the release of ET-1 into the circulation.

Topics: Adult; Endothelin-1; Female; Humans; Male; Melanocytes; Psoriasis; PUVA Therapy; Vitiligo

Little is known about the mechanisms involved in the dysfunction of melanocytes in vitiligo epidermis. It is hypothesized that some cytokine/receptor interactions may be affected, resulting in dysfunction and/or loss of melanocytes. This study has compared the expression of endothelin (ET)-1, the ET-1 receptor (ET(B)R), granulocyte macrophage colony stimulating factor (GM-CSF), stem cell factor (SCF), the SCF receptor (KIT protein), tyrosinase, and S100 alpha between lesional and non-lesional vitiligo epidermis. Analysis by reverse transcription-polymerase chain reaction (RT-PCR) and by western blotting for ET-1 and SCF unexpectedly demonstrated up-regulated expression of these cytokines in lesional vitiligo epidermis. Immunohistochemistry with antibodies to melanocyte markers revealed that at the edge of the lesional epidermis, melanocytes remain and express tyrosinase, S100 alpha and ET(B)R, but not KIT protein or melanocyte-specific microphthalmia-associated transcription factor (MITF-M). Quantitation of the staining revealed a slight or moderate decrease in the number of S100 alpha, tyrosinase, and ET(B)R-positive cells at the edge of the lesional epidermis. In contrast, the number of cells expressing KIT protein was markedly decreased at the edge of the lesional epidermis compared with the non-lesional epidermis. At the centre of the lesional epidermis, there was complete loss of melanocytes expressing KIT protein, S100 alpha, ET(B)R, and/or tyrosinase. Western blotting revealed down-regulated expression of c-kit and MITF-M proteins at the edge of the lesional epidermis in vitiligo. These findings suggest that reduction in the expression of KIT protein by melanocytes and its downstream effectors, including MITF-M, may be associated with the dysfunction and/or loss of melanocytes in vitiligo epidermis.

Topics: Adult; Aged; Antibody Specificity; Blotting, Western; DNA-Binding Proteins; Endothelin-1; Epidermis; Female; Gene Expression; Granulocyte-Macrophage Colony-Stimulating Factor; Humans; Male; Melanocytes; Microphthalmia-Associated Transcription Factor; Middle Aged; Oncogene Proteins; Proto-Oncogene Proteins c-kit; Receptor, Endothelin A; RNA, Messenger; Stem Cell Factor; Transcription Factors; Vitiligo

To investigate the effect of endothelin-1 (ET-1) on the adhesion and migration of melanocyte in vitro.. Human epidermal melanocytes that had been cultured and purified were treated with ET-1 and observed for adhesion to bovine serum fibronectin-coated culture dishes. Stem cell factor (SCF) and ET-1 treated cells were also examined for migration into micropore filters coated with the same protein.. Compared with the SCF group, ET-1 treated melanocytes were easier to adhere to the dishes and to be moved into the filters, especially when the concentration was 32 nmol/L. When the concentration of ET-1 was 128 nmol/L or more, it could inhibit the adhesion and migration of melanocyte. At any concentration of ET-1 except at 2 nmol/L, there was a significant difference between ET-1-treated and untreated melanocytes (P < 0.01) when the adhesion test was carried out. However, even at 2 nmol/ L ET-1, there was obviously increased migration compared with those of ET-1 untreated melanocytes and SCF-treated cells (P < 0.01).. ET-1 may influence the adhesion and migration of melanocyte, which can partly explain the capacity of ET-1 to regulate the melanocyte function in vitiligo lesions.

Topics: Cell Adhesion; Cell Movement; Cells, Cultured; Endothelin-1; Humans; Melanocytes; Skin; Vitiligo