Activation of the inducible nitric oxide synthase (iNOS)/nitric oxide (NO) pathway in keratinocytes has been reported to be associated with the pathogenesis of melanogenesis. Akt activation plays an important role in the activation of the transcription factor nuclear factor (NF)-κB and subsequent elevation of iNOS expression. In the present study, we highly detected both iNOS protein and Akt phosphorylation in keratinocytes of the basal layer of the epidermis at the junction with the dermis of melasma skin biopsy specimens, but not in normal skin tissues, from nine patients using immunohistological analysis. iNOS protein and phosphorylated Akt were co-localized in the lesional skins, and their levels were highly correlated (R2= 0.69). Furthermore, iNOS mRNA was also detected in an additional three skin biopsy specimens, but not in normal skin, by reverse transcription polymerase chain reaction. Our results describe that iNOS expression is elevated in human melasma lesions, probably via activation of the Akt/NF-κB pathway, indicating that NO production plays an important role in the mechanism of hyperpigmentation in human facial melasma.
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