Subtoxic levels hydrogen peroxide-induced expression of interleukin-6 by epidermal melanocytes.

Oxidative stress and autoimmune reaction are involved in the pathogenesis of vitiligo. Levels of hydrogen peroxide (HO) and interleukin-6 (IL-6), a proinflammation cytokine and a key factor in the pathogenesis of autoimmune diseases, have been reported to be elevated in vitiligo lesions. The objective of this study was to evaluate the effects of subtoxic levels of HO on the expression of IL-6 by cultured human epidermal melanocytes and to explore the relevant signal pathways. Cultured human melanocytes were stimulated with of HO at subtoxic levels. Levels of IL-6 protein in the medium and IL-6 mRNA in the cells were measured by IL-6 ELISA analysis and RT-PCR, respectively. NF-κB and phosphorylated p38 mitogen-activated protein kinase (MAPK), ERK and JNK in cells cultured with and without HO were measured by relevant ELISA kits. In cultured melanocytes, subtoxic levels of HO (30-300 μM) significantly increased the IL-6 mRNA and protein levels in a dose-dependent manner. NF-κB in nuclear extracts and phosphorylated p38 MAPK levels in cell lysates were significantly increased in HO treated cells. Pretreatment of cells with inhibitors of p38 MAPK (SB203580) and NF-κB (BAY11-7082), but not inhibitors of ERK (UO1026) and JNK (SP600125), abolished HO-induced expression of IL-6. HO-induced overexpression of IL-6 by melanocytes may be a molecular linkage for the oxidative stress and inflammatory/autoimmune reactions in vitiligo and may provide a novel target for the treatment of vitiligo. [ABSTRACT FROM AUTHOR]