Serum IL-2, -6, -17, -22, and TNF-α levels were measured by enzyme-linked immunosorbent assay (ELISA) in all patients and healthy controls, and their levels were correlated with the extent, duration, and activity of vitiligo.
We also investigated AHR-related cytokines and observed increased serum TNF-α concentration and diminished serum levels of IL-10 and TGF-β1 in vitiligo.
Therefore, our data demonstrated that dysregulated autophagy owing to the impairment of Nrf2-p62 pathway increase the sensitivity of vitiligo melanocytes to oxidative stress, thus promote the development of vitiligo.
These findings indicate that the C allele of rs35652124 located in the promoter region of Nrf2 gene is associated with protective effect on vitiligo in a Han Chinese population.
These data demonstrate that GR protects human melanocytes from H2O2‑induced oxidative damage via the Nrf2‑dependent induction of HO‑1, providing evidence for the application of GR in the treatment of vitiligo.
Therefore, impaired PI3K activation in keratinocytes in depigmented epidermis of vitiligo patients are vulnerable to apoptosis caused by ROS-generating chemicals due to reduced Nrf2 activation.
Taken together, our results show that simvastatin protects human melanocytes from H<sub>2</sub>O<sub>2</sub>-induced oxidative stress by activating Nrf2, thus supporting simvastatin as a potential therapeutic agent for vitiligo.
These data demonstrated that external stimuli (eg, oxidative stress) may trigger autocrine HMGB1 translocation and release by melanocytes, suppressing the expression of Nrf2 and downstream antioxidant genes to induce melanocyte apoptosis, and thereby participate in the pathological process of vitiligo.
Depigmented epidermis of vitiligo patients also showed lower levels of Nrf2 and phospho-PI3K but higher levels of ROS, TNF-ɑ, IL-1ɑ, and ROS with more TUNEL-positive cells.
Theories including reactive oxygen species model, Nrf2-antioxidant response element (ARE) pathway, WNT pathway, tyrosinase activity, biochemical, molecular, and cellular alterations have been hypothesized to explain vitiligo pathogenesis.
C478T, one of the MC1R SNPs studied in 108 fair-skinned vitiligo patients and in 70 fair-skinned healthy control individuals, showed a significant difference (P=0.0262, odds ratio [95% confidence interval]=3.6 [0.0046-0.1003]) in allele frequency between the two groups: the allele frequency was higher in the control group, suggesting protection against vitiligo.
We concluded that PMEL, MLANA), DCT, SOX10, TYRP1, and MC1R may play a role in vitiligo, among which TYRP1 and MC1R are regulated by forkhead box J2 (FOXJ2).
Recent investigations suggest an association between MC1R genotype and vitiligo, with preliminary evidence that a MC1R agonist, [Nle4-D-Phe7]-alpha-MSH, in combination with UVB, assists repigmentation.
Based on the SDTNBI method and experimental verification, Isorhamnetin and Kaempferide effectively increased melanogenesis by targeting the MC1R-MITF signaling pathway, MAPK signaling pathway, PPAR signaling pathway (PPARA, PPARD, PPARG), arachidonic acid metabolism pathway (ALOX12, ALOX15, CBR1) and serotonergic synapses (ALOX12, ALOX15) in the treatment of vitiligo from a network perspective.
Depigmented epidermis of vitiligo patients also showed lower levels of Nrf2 and phospho-PI3K but higher levels of ROS, TNF-ɑ, IL-1ɑ, and ROS with more TUNEL-positive cells.