Tissue level of nuclear factor-erythroid2-related factor2 and melanocyte-stimulating hormone in vitiligo patients

Background The pathogenesis of vitiligo is believed to depend on the presence of intrinsic/extrinsic metabolic defects in the melanocytes themselves or in the epidermal melanin unit, leading to oxidative stress, which further leads to melanocyte damage. The transcription factor, nuclear factor-erythroid 2-related factor 2 (Nrf-2), is a central regulator of the cellular antioxidant response and is a key factor for cytoprotection in various aspects. a-Melanocyte-stimulating hormone (aMSH) also plays an additional antioxidant role beyond its effect on the stimulation of melanogenesis. Objective To assess the level of Nrf-2 and aMSH in lesional and perilesional vitiligo skin and to study their relationship with the extent and activity of the disease. Patients and methods For 22 vitiligo patients, the vitiligo disease activity score and levels of lesional and nonlesional Nrf-2 and aMSH mRNA were determined by reverse transcription-PCR. Skin biopsies from 10 healthy volunteers served as controls for Nrf-2 and aMSHmRNA levels in normal skin. Results Lesional skin of vitiligo patients showed a significantly lower expression of Nrf-2 mRNA levels in comparison with nonlesional biopsies from the patients and with normal skin of the controls (P =0.001 and 0.000, respectively). Moreover, Nrf-2 mRNA in nonlesional skin of patients was significantly lower than that in the controls (Po0.01). The same trend was found in the levels of aMSH mRNA, which were significantly decreased in the lesional and perilesional biopsies versus the control group (P= 0.000 and 0.000). No significant correlation was detected between the levels of Nrf-2 mRNA and the levels of aMSH mRNA in lesional vitiligo skin. The levels of Nrf-2 and aMSH mRNA were not affected by the activity of the disease, presence of stress, or the extent of the disease. Conclusion The reduction of both Nrf-2 and aMSH mRNA levels in vitiligo lesions may play a role in the pathogenesis of vitiligo; yet, their levels are not markers of disease activity or severity. Moreover, the downregulation of their levels in perilesional skin of vitiligo patients may be a requisite for disease initiation when they reach levels that allow loss of self-tolerance.