Vitiligo and Epidermal Microenvironment: Possible Involvement of Keratinocyte-Derived Cytokines

Moretti, Silvia; Spallanzani, Adelina; Amato, L.; Hautmann, Giuseppe; Gallerani, Isabella; Fabbri, Paolo

doi:10.1001/archderm.138.2.273

Cited by 51 publications

(37 citation statements)

References 5 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Whatever hypothesis is considered, however, the pivotal role of the melanocyte in the pathogenesis of the disease is still under debate. Recent experimental data underline the complex interactions that exist between melanocytes and other typical skin cells, keratinocytes in particular (28). Many studies have shown that patients display varying extents of cellular vacuolation and cellular debris in epidermal keratinocytes (2,26).…”

mentioning

confidence: 99%

The Involvement of Smac/DIABLO, p53, NF-kB, and MAPK Pathways in Apoptosis of Keratinocytes from Perilesional Vitiligo Skin: Protective Effects of Curcumin and Capsaicin

Becatti

Prignano²,

Fiorillo³

et al. 2010

Antioxidants & Redox Signaling

View full text Add to dashboard Cite

Oxidative stress has been suggested as the initial pathogenetic event in melanocyte degeneration in vitiligo. Our previous results indicate that keratinocytes from perilesional skin show the features of damaged cells. In the present study, biopsies were taken from the perilesional skin of 12 patients suffering from nonsegmental vitiligo. The intracellular pathways involved in keratinocyte damage and apoptosis and the antioxidant protection of curcumin and capsaicin in these cells were investigated. In keratinocytes from perilesional vitiligo skin, we observed high levels of activated p38, NF-kB p65 subunit, p53, and Smac=DIABLO proteins. In contrast, low levels of ERK phosphorylation were present. To investigate the relationship between these pathways, we used specific inhibitors and evaluated the alteration of each pathway. For the first time, our study demonstrates the pivotal role of p38 MAP kinase as an upstream signal of perilesional keratinocyte damage, and the important contribution of p38 and NF-kB on p53 accumulation. Curcumin and capsaicin also increase ERK phosphorylation, thus inhibiting apoptosis. Moreover, pretreatment with such natural antioxidants inhibited caspase activation, increased total antioxidant capacity, repressed intracellular ROS generation and lipid peroxidation, and improved mitochondrial activity. These results suggest that antioxidants might represent an alternative approach to protect against vitiligo progression. Antioxid. Redox Signal. 13, 1309-1321.

show abstract

mentioning

confidence: 99%

The Involvement of Smac/DIABLO, p53, NF-kB, and MAPK Pathways in Apoptosis of Keratinocytes from Perilesional Vitiligo Skin: Protective Effects of Curcumin and Capsaicin

Becatti

Prignano²,

Fiorillo³

et al. 2010

Antioxidants & Redox Signaling

View full text Add to dashboard Cite

show abstract

“…4). In lesional skin of active NSV, a higher expression of cytokines that inhibit melanocytes (in particular TNF-a) and a lower expression of cytokines with stimulating activity toward pigment cells (SCF, bFGF, GM-CSF) were demonstrated, suggesting that a modification of the epidermal cytokines is involved in vitiligo pathogenesis (41)(42). Since TNF-a is capable of inducing ROS production from mitochondria (34), the higher expression of this cytokine in lesional NSV skin may represent a link with the metabolic theory and justify the attribution of the main target to mitochondria.…”

Section: New Proposals On the Pathogenesismentioning

confidence: 99%

Focus on Vitiligo: A Generalized Skin Disorder

et al. 2006

Self Cite

View full text Add to dashboard Cite

Vitiligo is an acquired pigmentation disorder due to a disappearance of functioning melanocytes from the epidermis and clinically characterized by achromic patches, often spreading over time. It is still not fully understood how melanocytes disappear in vivo, inducing these peculiar lesions. There are three major hypotheses for the pathogenesis of the disease: the autoimmune hypothesis considers that the disappearance of melanocytes is due to an autoimmune effector mechanism, the neural hypothesis suggests that an accumulation of neurochemical substances is able to damage epidermal melanocytes, and the metabolic hypothesis indicates that an increased sensitivity of melanocytes to oxidative stress is the crucial factor of the disease. Besides these well accepted hypotheses there are also some new interpretations based on a defective adhesion of melanocytic cells, an imbalance in the epidermal production of cytokines and an altered expression of melanocyte receptors. All these theories seem to be based on convincing evidence, indicating that they may contribute in variable proportions to the disease. There is also reasonable evidence at present that vitiligo potentially involves the whole integument, suggesting that it is a generalized skin disorder probably including different cell types during the active phase of the disease. It appears that the different theories may integrate with each other, supporting the concept that in vitiligo there is a final common step, i.e. a loss of pigment in the epidermis as well as different, possibly interacting, pathways leading up to this conclusive result.

show abstract

“…6 TNF-a inhibits melanocyte activity. 15 It has been found in murine models that TNF-a may either exert a growthpromoting activity on fibroblasts, endothelial cells, or keratinocytes or induce complete necrosis of such cells at elevated levels. 16 TNF-a has been shown to maintain Langerhans cells in culture as well as diminish Langerhans cells after intradermal injection of the cytokine.…”

Section: Tumor Necrosis Factor-alpha (Tnf-a)mentioning

confidence: 99%

“…Psoriasis is more common in Crohn's patients (10% vs. 2% in the general population), and it was initially observed that patients treated with infliximab for Crohn's disease exhibited improvement of psoriatic lesions. 15 Although infliximab is not yet indicated for use in psoriasis, psoriatics other than those with Crohn's disease have been treated with infliximab with generally good efficacy, and there seems promise that infliximab may be an effective agent in the treatment of severe plaque-type psoriasis. 50,51 Psoriatic arthritis is a complication of psoriasis that occurs in about 5% to over 30% of patients, 52 with infliximab having a good potential as treatment for this disease as well.…”

Section: Panniculitismentioning

confidence: 99%

“…53,54 Systemic therapy may be the best choice for severe psoriasis because of the psychosocial effects and impaired quality of life. 15 Infliximab may produce a durable response, lasting more than 10 months from the third infusion (after 6 weeks), in patients who respond well. 55 The duration of remission of psoriasis after treatment with infliximab is comparable to that of other remittent, antipsoriatic therapies (such as PUVA).…”

Section: Panniculitismentioning

confidence: 99%

See 1 more Smart Citation