interleukin-8 and Vitiligo

Vitiligo is a depigmenting disorder resulting from loss of functional melanocytes in the skin. Variety of inflammatory mediators participate in the regulation of melanogenesis in melanocytes: interleukin-18 (IL-18), interleukin-33, granulocyte-macrophage colony stimulating factor, interferon-γ, prostaglandin E2 have the effect of promoting melanogenesis, while interleukin-1 (IL-1), interleukin-4, interleukin-6, interleukin-17 and tumor necrosis factor can inhibit melanogenesis.. Evaluation of IL-1α and IL-18 levels in peripheral blood in patients with vitiligo compared to healthy controls.. Fifty patients aged 18-81 with vitiligo participated in the study. The control group consisted of 38 healthy people. Venous blood samples were obtained from each participant. Serum IL-1α and IL-18 concentrations were determined using the enzyme-linked immunoabsorbent assay (ELISA).. Among patients with vitiligo, the mean concentration of IL-1α was 0.13 (± 0.535) pg/mL, while in the control group it was 0.51 (± 1.51). There were no statistically significant differences in IL-1α concentrations between patients in the study group compared to the control group (p > 0.05). In the study group, the mean IL-18 concentration was 141.05 (± 136.33) pg/mL vs 137.33 (± 105.83) pg/mL in the controls. There were no statistically significant differences in IL-18 concentrations between patients in the study group compared to the controls (p > 0.05). In the Spearman correlation test, no correlation was confirmed between IL1α and IL-18 concentrations in the group of patients with vitiligo vs healthy people.. There is no correlation between Il-1 and Il-18 concentration in the blood sera of patients with vitiligo.

Topics: Case-Control Studies; Humans; Interleukin-1; Interleukin-18; Interleukin-1alpha; Interleukin-8; Vitiligo

Toll-like receptors (TLRs) are expressed on human melanocytes, and play an important role in innate and acquired immunity. The role of TLRs in the pathogenesis of vitiligo has not been fully described.. To investigate the expression of TLRs in melanocytes from patients with vitiligo and healthy controls (HCs).. Primary cultured vitiligo and control melanocytes were obtained from perilesional normal skin of patients with generalized vitiligo and HCs. TLRs mRNA expression in melanocytes were determined by real-time reverse transcription PCR and protein expression by western blotting. Apoptosis was analysed using an annexin V-fluorescein isothiocyanate apoptosis detection kit, and tyrosinase activity and melanin content were measured by a modified dopachrome and colorimetric method. Interleukin (IL)-6, IL-8 and soluble cell adhesion molecule (sICAM)-1 expression were measured by ELISA.. In vitiligo melanocytes, compared with control melanocytes, apoptosis rate, expression of TLR7 and TLR9 mRNA and protein, and production of IL-8, IL-6 and sICAM-1 were significantly increased, whereas tyrosinase activity and melanin content were significantly decreased.. Our results suggest that the increased expression of TLR7 and TLR9 might correlate with melanocyte dysfunction in vitiligo.

Topics: Adult; Apoptosis; Blotting, Western; Cell Adhesion Molecule-1; Cells, Cultured; Epidermal Cells; Female; Humans; Interleukin-6; Interleukin-8; Male; Melanins; Melanocytes; Middle Aged; Monophenol Monooxygenase; Pilot Projects; Real-Time Polymerase Chain Reaction; Toll-Like Receptor 7; Toll-Like Receptor 9; Vitiligo

Topics: Adolescent; Adult; Aged; Case-Control Studies; CD8-Positive T-Lymphocytes; Cell Line; Chemokine CCL5; Chemokine CXCL10; Child; Child, Preschool; Epidermis; Female; Humans; Interferon-gamma; Interleukin-8; Male; Middle Aged; Pilot Projects; Tumor Necrosis Factor-alpha; Vitiligo; Young Adult

Vitiligo is a disorder of depigmentation, for which the pathogenesis is as yet unclear. Interleukin (IL)-8 (CXCL8) is a key inflammatory chemokine. We investigated the regulation of IL-8 production in human melanocytes, and the IL-8 serum levels and skin gene expression in patients with vitiligo and in controls. Cultured melanocytes were stimulated for 24 h with tumour necrosis factor (TNF) 100 ng/mL and IL-1β 10 ng/mL, with or without pretreatment with luteolin 50 μmol/L for 30 min, and IL-8 release was measured by ELISA. Serum cytokines were measured by a microbead array. Skin biopsies were taken from healthy subjects (n = 14) as well as from marginal lesional and nonlesional skin from patients with vitiligo (n = 15). IL-8 gene expression was evaluated by quantitative real time PCR. Both TNF and IL-1β stimulated significant IL-8 release (P < 0.01) from melanocytes, whereas pretreatment with luteolin significantly inhibited this effect (P < 0.01). IL-8 gene expression was significantly increased in vitiligo compared with control skin (P < 0.05). IL-8 may be involved in vitiligo inflammation. Inhibition by luteolin of IL-8 release could be useful for vitiligo therapy.

Topics: Adult; Case-Control Studies; Cells, Cultured; Enzyme-Linked Immunosorbent Assay; Female; Gene Expression Profiling; Humans; Interleukin-1beta; Interleukin-6; Interleukin-8; Luteolin; Male; Melanocytes; Middle Aged; Skin; Tumor Necrosis Factor-alpha; Vascular Endothelial Growth Factor A; Vitiligo

Rhododendrol, an inhibitor of melanin synthesis developed for lightening/whitening cosmetics, was recently reported to induce a depigmentary disorder principally at the sites of repeated chemical contact. Rhododendrol competitively inhibited mushroom tyrosinase and served as a good substrate, while it also showed cytotoxicity against cultured human melanocytes at high concentrations sufficient for inhibiting tyrosinase. The cytotoxicity was abolished by phenylthiourea, a chelator of the copper ions at the active site, and by specific knockdown of tyrosinase with siRNA. Hence, the cytotoxicity appeared to be triggered by the enzymatic conversion of rhododendrol to active product(s). No reactive oxygen species were detected in the treated melanocytes, but up-regulation of the CCAAT-enhancer-binding protein homologous protein gene responsible for apoptosis and/or autophagy and caspase-3 activation were found to be tyrosinase dependent. These results suggest that a tyrosinase-dependent accumulation of ER stress and/or activation of the apoptotic pathway may contribute to the melanocyte cytotoxicity.

Topics: Agaricales; Apoptosis; Butanols; Caspase 3; Catalytic Domain; Cell Survival; Cells, Cultured; Chelating Agents; Copper; Endoplasmic Reticulum Stress; Enhancer Elements, Genetic; Enzyme-Linked Immunosorbent Assay; Gene Expression Profiling; Gene Expression Regulation; Humans; Hypopigmentation; Inhibitory Concentration 50; Interleukin-8; Melanocytes; Monophenol Monooxygenase; Phenylthiourea; Pigmentation; Reactive Oxygen Species; RNA, Small Interfering; Skin Lightening Preparations; Up-Regulation; Vitiligo

Vitiligo is characterized by depigmented skin patches caused by loss of epidermal melanocytes. Oxidative stress may have a role in vitiligo onset, while autoimmunity contributes to disease progression. In this study, we sought to identify mechanisms that link disease triggers and spreading of lesions. A hallmark of melanocytes at the periphery of vitiligo lesions is dilation of the endoplasmic reticulum (ER). We hypothesized that oxidative stress results in redox disruptions that extend to the ER, causing accumulation of misfolded peptides, which activates the unfolded protein response (UPR). We used 4-tertiary butyl phenol and monobenzyl ether of hydroquinone, known triggers of vitiligo. We show that expression of key UPR components, including the transcription factor X-box-binding protein 1 (XBP1), is increased following exposure of melanocytes to phenols. XBP1 activation increases production of immune mediators IL6 and IL8. Co-treatment with XBP1 inhibitors reduced IL6 and IL8 production induced by phenols, while overexpression of XBP1 alone increased their expression. Thus, melanocytes themselves produce cytokines associated with activation of an immune response following exposure to chemical triggers of vitiligo. These results expand our understanding of the mechanisms underlying melanocyte loss in vitiligo and pathways linking environmental stressors and autoimmunity.

Topics: Autoimmunity; Cell Line; DNA-Binding Proteins; Gene Expression; Humans; Hydroquinones; Infant, Newborn; Interleukin-6; Interleukin-8; Melanocytes; Oxidative Stress; Phenols; Regulatory Factor X Transcription Factors; Skin; Transcription Factors; Unfolded Protein Response; Up-Regulation; Vitiligo; X-Box Binding Protein 1

Vitiligo is characterized by a substantial loss of functional melanocytes in the epidermis and sometimes in hair follicles. Genetic and pathophysiological studies have provided strong evidence that vitiligo is a polygenetic, multifactorial disorder. The key roles of oxidative stress within melanocytes and anti-melanocyte immune responses have been addressed in many studies, but the relationship between these mechanisms remains unclear. In this issue, Toosi et al. report the upregulation of IL-6 and IL-8 after the activation of the unfolded protein response (UPR) following exposure of melanocytes to phenols. Their results shed light on the missing link between oxidative stress and immune responses in vitiligo.

Topics: Humans; Interleukin-6; Interleukin-8; Melanocytes; Unfolded Protein Response; Vitiligo

Although the cause of vitiligo is unknown, an autoimmune theory has been proposed, and there is now convincing evidence that cytokines have an important role in pathogenesis of autoimmunity.. To study the possible role of interleukin-1, beta (IL-1 beta), interleukin-6 (IL-6), interleukin-8 (IL-8), tumor necrosis factor-alpha (TNF-alpha) and granulocyte-macrophage colony stimulating factor (GM-CSF) in the pathogenesis of vitiligo.. The authors measured the serum levels of the above-mentioned cytokines from 50 patients with the vitiligo compared with 20 healthy volunteers, employing the method of radioimmunoassay.. The results showed that the serum levels of both IL-6 and GM-CSF of the patients with both focal type and generalized type of vitiligo, and the serum level of IL-1 beta of the generalized type,were significantly, higher than those of normal controls in the patients with segmental vitiligo, the serum levels of all the cytokines tested were not significantly different from those of the normal controls. The GM-CSF levels of both focal type and generalized type, and the IL-6 level of the generalized type in progressive stage were significantly higher than those in stable state.. It is speculated that IL-6 and GM-CSF may be involved in the autoimmune mechanism of non-segmental vitiligo. However, more evidence is required before a definite conclusion can be drawn.

Topics: Adolescent; Adult; Aged; Case-Control Studies; Child; Female; Granulocyte-Macrophage Colony-Stimulating Factor; Humans; Interleukin-1; Interleukin-6; Interleukin-8; Male; Middle Aged; Tumor Necrosis Factor-alpha; Vitiligo

An immunologic hypothesis is currently proposed as a possible pathogenesis of nonsegmental-type vitiligo. IgG antibodies against melanocyte surface antigens exist in the serum of patients with vitiligo vulgaris. IgG anti-melanocyte antibodies were reported to induce melanocyte damage in vitro by a complement-mediated mechanism and antibody-dependent cellular cytotoxicity. Perilesional melanocytes express major histocompatibility complex class II antigens and a higher intercellular adhesion molecule-1 compared with those in normal skin. The purpose of this study was to determine the role of IgG anti-melanocyte antibodies in the inappropriate expression of major histocompatibility complex class II antigens and intercellular adhesion molecule-1 on melanocytes. IgG anti-melanocyte antibody samples were purified from the individual serum of patients with active vitiligo. After incubation of IgG anti-melanocyte antibodies with cultured melanocytes, the results revealed: (i) IgG anti-melanocyte antibody stimulated HLA-DR expression on melanocytes; (ii) intercellular adhesion molecule-1 expression on melanocytes was significantly induced by IgG anti-melanocyte antibodies; and (iii) IgG anti-melanocyte antibodies induced an increase in interleukin-8 release from melanocytes. The major histocompatibility complex class II molecules expressed in melanocytes can present antigens to CD4 helper cells as antigen-presenting cells and elicit an immune response. Intercellular adhesion molecule-1 is an important adhesion molecule involved in leukocyte and parenchymal cell interaction and thus plays an essential part in immunologic and inflammatory reactions. It is reasonable to speculate that abnormal expressions of HLA-DR and intercellular adhesion molecule-1 on melanocytes by IgG anti-melanocyte antibodies would present vitiligo antigens and allow the antigen-specific immune effector cell attack that results in melanocytotoxicity.

Topics: Antibodies, Anti-Idiotypic; Female; HLA-DR Antigens; Humans; Immunoglobulin G; Intercellular Adhesion Molecule-1; Interleukin-8; Male; Melanocytes; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; Vitiligo

The purpose of this study was to clarify the relationship between the cellular and humoral immune components in the pathogenesis of vitiligo vulgaris. By using cytokines as indicators of peripheral mononuclear cell (MNC) function, we compared the effects of phytohemagglutinin (PHA) and purified IgG on MNCs derived from patients suffering from active vitiligo with those from normal controls. The results revealed (i) a significant increase in spontaneous production of IL-6 and IL-8 in patients; (ii) PHA, purified IgG from patients (IgG-anti-MC), or IgG from normal controls (N-IgG) induced a significant increase in IL-6 but diminished GM-CSF, TNF-alpha, and IFN-gamma release in patients; and (iii) IgG-anti-MC brought about a significantly higher stimulatory effect on IL-1beta and IFN-gamma production than N-IgG in normal controls. Immunologically, IL-6 can enhance melanocyte ICAM-1 expression, which may increase leukocyte-melanocyte attachment and cause melanocyte damage in vitiligo. A decrease in GM-CSF (an intrinsic growth factor for melanocyte) production may retard recovery from vitiligo by checking the proliferation of surviving melanocytes. A significant decrease in TNF-alpha and IFN-gamma production may partially explain the reduced inflammatory reaction in vitiliginous lesions. That IgG-anti-MC stimulates an increase in IL-1beta and IFN-gamma production in controls suggests that IgG-anti-MC may play a role in melanocyte destruction mediated by monocytes.

Topics: Antibodies; Female; Granulocyte-Macrophage Colony-Stimulating Factor; Humans; Immunoglobulin G; Interferon-gamma; Interleukin-6; Interleukin-8; Interleukins; Leukocytes, Mononuclear; Male; Melanocytes; Phytohemagglutinins; Tumor Necrosis Factor-alpha; Vitiligo