Stimulated human melanocytes express and release interleukin-8, which is inhibited by luteolin: relevance to early vitiligo

Abstract

Summary Vitiligo is a disorder of depigmentation, for which the pathogenesis is as yet unclear. Interleukin (IL)-8 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 reverse transcriptase 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.

Inhibitory effects of wild bitter melon leaf extract on Propionibacterium acnes-induced skin inflammation in mice and cytokine production in vitro

“…15 Luteolin has been demonstrated to be a potent antiinflammatory agent. 16,17 However, little is known about its effect on P. acnes-induced inflammatory reactions. To prove A control experiment without P. acnes treatment was conducted in parallel.…”

Differential expression of inflammatory cytokines and chemokines in lipopolysaccharide‐stimulated melanocytes from lightly and darkly pigmented skin

“…The chemokine is involved in the acute inflammatory response in vivo and exhibits a chemotactic activity for neutrophils, T cells, fibroblasts, endothelial cells and melanocytes in vitro . Miniati et al observed increased release of CXCL8 from human melanocytes in response to TNF‐α and IL‐1β, and elevated CXCL8 gene expression in the lesional skin of patients with new‐onset and active vitiligo. Moreover, CXCL8 has been reported to induce oxidative stress, leading indirectly to both keratinocyte and melanocyte apoptosis in vitiligo.…”

“…They have the capacity to phagocytosis and are capable of antigen processing and presentation . In response to various stimuli, melanocytes can produce and release soluble mediators of inflammation, such as nitric oxide, interleukin (IL)‐1α, IL‐1β, IL‐6, IL‐8, tumor necrosis factor (TNF)‐α and interferon (INF)‐β, which could affect melanocytes themselves or/and other cells of the epidermis, contributing to a local immune response. Melanocytes also produce several immunosuppressive molecules, including proopiomelanocortin‐derived adrenocorticotropic hormone and α‐melanocyte‐stimulating hormone, corticotropin‐releasing hormone, cortisol, corticosterone and other steroids …”

Enhanced bleaching treatment: opportunities for immune‐assisted melanocyte suicide in vitiligo

“…This results in increased production of IL‐6 and IL‐8 by melanocytes . Increased IL‐8 expression was likewise found in skin of patients with active disease . Overproduction of pro‐inflammatory cytokines and decreased availability of immunosuppressive regulatory T cells, combined with increased abundance of cytotoxic T cells, all contribute to depigmentation.…”