We investigated whether the tumor necrosis factor-a (TNF-α) promoter -238 A/G and -308 A/G polymorphisms are associated with rheumatoid arthritis (RA) and vitiligo susceptibility.
Additionally, enrichment analysis suggested that targets of KBL on vitiligo were mainly clustered into multiple biological processes (associated with DNA translation, lymphocyte differentiation and activation, steroid biosynthesis, autoimmune and systemic inflammatory reaction, neuron apoptosis, and vitamin deficiency) and related pathways (TNF, JAK-STAT, ILs, TLRs, prolactin, and NF-<i>κ</i>B), indicating the underlying mechanisms of KBL on vitiligo.
The frequency of allele A (TNF-α 2-allele) was significantly higher and that of allele G (TNF-α 1-allele) was lower in vitiligo patients compared to controls, indicating an association of allele A with susceptibility to vitiligo in Saudi patients.
The study's findings demonstrate that the studied hypopigmented (vitiligo, hypopigmented MF, hypopigmented TV) disorders show similar changes in their cutaneous microenvironment with increased TNF-α and decreased bFGF mRNA expression.
Data for a total of 1505 vitiligo cases and 2253 controls from five case-control studies concentrating on the association between TNF-α-308 G/A polymorphism and vitiligo were included in this meta-analysis.
The expression levels of IL-6, IL-17 and TNF-α in patients with progressive vitiligo were significantly higher than those in patients with stable vitiligo (P<0.05).
Since the presence of A nucleotide at position -308 of TNF-alpha gene is associated with increased cytokine production, therefore, the higher frequency of TNF-alpha -308 A allele in vitiligo patients compared to controls may be considered as a genetic susceptibility factor towards the development of vitiligo.
Our aim was to investigate the role of IFN-γ expression and polymorphism in vitiligo susceptibility and whether intercellular adhesion molecule-1 (ICAM-1), tumor necrosis factor (TNF)-α, and TNF-β play a role in vitiligo pathogenesis as important inflammatory parameters.
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.
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.