- Inflammation drives nitric oxide synthase 2 expression by γδ T cells and affects the balance between melanoma and vitiligo associated melanoma. [Journal Article]
- OOncoimmunology 2018; 7(9):e1484979
- The high expression of inducible nitric oxide synthase (NOS2) by myeloid-derived suppressor cells (MDSCs) is a key mechanism of immune evasion in cancer. Recently we reported that NOS2 is also expres...
The high expression of inducible nitric oxide synthase (NOS2) by myeloid-derived suppressor cells (MDSCs) is a key mechanism of immune evasion in cancer. Recently we reported that NOS2 is also expressed by γδ T cells in melanoma, contributing to their polarization towards a pro-tumor phenotype. The molecular mechanisms underlying regulation of NOS2 expression in tumor-induced γδ T cells remain unexplored. By using the model of mice transgenic for the ret oncogene (Ret mice) that develops a spontaneous metastatic melanoma, we evidence that interleukin (IL)-1β and IL-6 drive NOS2 expression in γδ T cells. Indeed, their in vivo neutralization lessens the γδ T cell capacity to produce not only NOS2, but also IL-17 involved in the recruitment of MDSCs at the primary tumor site. The treatment also delayed tumor cell dissemination and induced vitiligo in a significant proportion of Ret mice. Interestingly, Ret mice developing a less aggressive melanoma, characterized by the spontaneous development of a concomitant autoimmune vitiligo, exhibit a weaker concentration of inflammatory cytokines and a reduction of tumor infiltrating γδ T cells expressing NOS2, when compared to Ret mice without any signs of vitiligo. Overall our results support that the level of inflammation at the tumor site regulates NOS2 expression by γδ T cells and the development of vitiligo associated melanoma.
- Low-dose UVB therapy is comparable with conventional UVB phototherapy for treatment of vitiligo: A pilot study. [Letter]
- JDJ Dermatol Sci 2018 Aug 31
- Potential anti-vitiligo properties of cynarine extracted from Vernonia anthelmintica (L.) Willd. [Journal Article]
- IJInt J Mol Med 2018 Sep 06
- Vitiligo is a depigmentation disorder of the skin. It is primarily caused by the destruction of melanocytes or obstruction of the melanin synthesis pathway. Melanin is a type of skin pigment that det...
Vitiligo is a depigmentation disorder of the skin. It is primarily caused by the destruction of melanocytes or obstruction of the melanin synthesis pathway. Melanin is a type of skin pigment that determines skin color. The seeds of Vernonia anthelmintica (L.) Willd (Kaliziri) are used for treating skin diseases including vitiligo in traditional Uyghur medicine. 1,5‑Dicaffeoylquinic acid (1,5‑diCQA) is a natural polyphenolic compound widely distributed in plants and extracted from Kaliziri seeds. Therefore, in the present study, the effect of 1,5‑diCQA on melanin synthesis in B16 cell was evaluated, and its molecular mechanism was explored. The results indicated that 1,5‑diCQA treatment of B16 cells stimulated an increase of intracellular melanin level and tyrosinase (TYR) activity without cytotoxicity. Reverse transcription quantitative polymerase chain reaction results also indicated that 1,5‑diCQA may markedly improve the protein expression and RNA transcription of microphthalmia‑associated transcription factor (MITF), melanogenic enzyme Tyr, tyrosinase‑related protein 1 (TRP 1) and tyrosinase‑related protein 2 (TRP 2). Additional results identified that 1,5‑diCQA may promote the phosphorylation of p38 mitogen‑activated protein kinase (p38 MAPK) and extracellular signal‑regulated kinase (ERK) MAPK. Notably, the increased levels of intracellular melanin synthesis and tyrosinase expression induced by 1,5‑diCQA treatment were significantly attenuated by the protein kinase A (PKA) inhibitor H‑89. Intracellular cyclic adenosine monophosphate (cAMP) concentration and phosphorylation of cAMP‑response element binding protein was increased following 1,5‑diCQA treatment. These results indicated that 1,5‑diCQA stimulated melanogenesis via the MAPK and cAMP/PKA signaling pathways in B16 cells, which has potential therapeutic implications for vitiligo.
- Morphological Classification System of Hair Regrowth Patterns in Alopecia Areata Patches: DIMT Classification. [Journal Article]
- JEJ Eur Acad Dermatol Venereol 2018 Sep 17
- Alopecia areata (AA) is an autoimmune disease causing non-scarring hair loss. In many cases, regrowth of hair can be expected either with or without treatment. In vitiligo, which has similarities in ...
Alopecia areata (AA) is an autoimmune disease causing non-scarring hair loss. In many cases, regrowth of hair can be expected either with or without treatment. In vitiligo, which has similarities in pathogenesis with AA, repigmentation patterns have been classified into 5 distinct patterns: diffuse, marginal, perifollicular, combined, and medium-spotted. This article is protected by copyright. All rights reserved.
- Prescribing Home Narrowband UVB Phototherapy: A Review of Current Approaches. [Journal Article]
- JCJ Cutan Med Surg 2018 Sep 15; :1203475418800947
- Conventional, full-body phototherapy equipment is costly and therefore patients are usually treated in dermatology centres. Such office-based therapy is often not feasible for those patients who live...
Conventional, full-body phototherapy equipment is costly and therefore patients are usually treated in dermatology centres. Such office-based therapy is often not feasible for those patients who live far away from a phototherapy centre due to lost time and wages, inability to travel because of extensive skin disease, or prohibitive travel costs. Home phototherapy has emerged as a modality that meets the needs of those patients. Our aim was to review available studies on UV sources, treatment protocols, efficacy, and safety of home phototherapy. A literature review was conducted on PubMed using the terms "home" AND "phototherapy" AND ("guide" OR "approach" OR "review" OR "protocol"). From the data extracted, narrowband UVB (311 nm) offers the best balance between safety and efficacy and is recommended for home phototherapy by most authors. Treatment is safe and possible adverse effects are related to overexposure (erythema, blistering). The usual treatment protocol was administering treatments on alternating days, including weekends, with dosing based on the patient's Fitzpatrick skin type. We also provide information on the available home phototherapy systems in Canada and their reimbursement. Home phototherapy is underused in Canada. Narrowband UVB phototherapy sources equipped with a 3-dimensional panel provides a practical and safe option.
- Controversial Issues In Vitiligo patients: a review of old and recent treatments. [Review]
- DTDermatol Ther 2018 Sep 17; :e12745
- Vitiligo is quite a common hypopigmentary disorder, which may affect both children and adults with important psychological effects due to the well-known leopard skin-like appearance. The authors summ...
Vitiligo is quite a common hypopigmentary disorder, which may affect both children and adults with important psychological effects due to the well-known leopard skin-like appearance. The authors summarize in this paper the published evidence on vitiligo with particular interest on the controversial aspects of the disease, such its definition and the available treatments. This article is protected by copyright. All rights reserved.
- Identification of the Risk HLA-A Alleles and Autoantigen in Han Chinese Vitiligo Patients and the Association of CD8+T Cell Reactivity with Disease Characteristics. [Journal Article]
- MSMed Sci Monit 2018 Sep 16; 24:6489-6497
- CONCLUSIONS: Our findings showed that the HLA-A*02: 01 allele was the major risk HLA-A allele, and 2 gp100 modified peptides were identified as autoantigens and were found to be closely related to disease characteristics which might play a critical role in Han Chinese vitiligo patients.
- Skin diseases associated with atopic dermatitis. [Journal Article]
- CDClin Dermatol 2018 Sep - Oct; 36(5):631-640
- Atopic dermatitis is a common chronic pruritic inflammatory skin disorder, characterized by an abnormal skin barrier, immune dysfunction, and an altered skin microbiome. Atopic dermatitis may be seen...
Atopic dermatitis is a common chronic pruritic inflammatory skin disorder, characterized by an abnormal skin barrier, immune dysfunction, and an altered skin microbiome. Atopic dermatitis may be seen in conjunction with a variety of other skin disorders due to the complex pathogenesis of atopic dermatitis, involving genetic and environmental factors that are associated with immune dysfunction, barrier defects, and altered skin microbiomes. Skin disorders associated with atopic dermatitis include diseases sharing similar genetic origins like ichthyosis vulgaris, infectious diseases such as impetigo, and eczema herpeticum, in addition to the cutaneous autoimmune diseases, alopecia areata, and vitiligo. Atopic dermatitis is also often linked to such benign conditions as pityriasis alba and keratosis pilaris. This review discusses the cutaneous comorbidities of atopic dermatitis and their relationship via their occurrence in conjunction with atopic dermatitis.
- ROS-challenged keratinocytes as a new model for oxidative stress-mediated skin diseases. [Journal Article]
- JCJ Cell Biochem 2018 Sep 14
- In the current study, the effects of the reactive oxygen species (ROS) generator 2,2'-azobis(2-amidinopropane) dihydrochloride (AAPH) on extracellular and intracellular ROS production in human kerati...
In the current study, the effects of the reactive oxygen species (ROS) generator 2,2'-azobis(2-amidinopropane) dihydrochloride (AAPH) on extracellular and intracellular ROS production in human keratinocytes (HACAT) were studied. AAPH is a water-soluble compound able to generate ROS at known and constant rates at 37°C. The short treatment (2 h) with AAPH brought a significant dose-dependent increase in NADPH oxidase activity in intact keratinocytes. The long-term treatment (24 h) with AAPH led to a persistent increase in NADPH oxidase activity for up to 48 hour following the AAPH removal from cell incubation medium. ROS and nitric oxide levels, lipoperoxidation, intracellular calcium, mitochondrial superoxide production, and membrane potential were significantly modified in AAPH-treated HACAT. Superoxide dismutase (SOD) and/or catalase addition to HACAT revealed that untreated keratinocytes produce mostly superoxide anion (O 2- ), while AAPH-treated keratinocytes overproduce hydrogen peroxide (H 2 O 2 ) in extracellular medium. H 2 O 2 is particularly stable and plays important roles in several cell signaling pathways. Taken together, our findings suggest a cost-effective and easily reproducible in vitro model of stressed human keratinocytes releasing significantly elevated ROS amounts in extracellular medium with respect to control keratinocytes. The possible application of the proposed model for keratinocytes-melanocytes cross-talk studies is also suggested. The model of AAPH-stressed human keratinocytes described here can represent a useful tool for redox cross-talk studies between keratinocytes and other skin cell types, and applied for researches regarding skin pathologies associated with oxidative stress.
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- JAK-STAT signaling pathway inhibition: a role for treatment of various dermatologic diseases. [Journal Article]
- SCSemin Cutan Med Surg 2018; 37(3):198-208
- Cutaneous inflammatory conditions such as psoriasis, atopic dermatitis, alopecia areata, vitiligo, and connective tissue diseases often remain a challenge to treat. Although there is an in-depth unde...
Cutaneous inflammatory conditions such as psoriasis, atopic dermatitis, alopecia areata, vitiligo, and connective tissue diseases often remain a challenge to treat. Although there is an in-depth understanding of the clinical presentation of these diseases, much less is known regarding the pathophysiology. This has limited the effective treatment options for patients. A more detailed understanding of the pathogenesis of each disease will lead to newer targeted medications with less morbidity. Though there are different pathways involved in these diseases, the Janus Kinase (JAK)-Signal Transducer and Activator of Transcription proteins (STAT) signaling pathway is common to them all. Therefore, this review article endeavors to substantiate the immunopathology and clinical utility of the JAK inhibitors as treatments for different chronic inflammatory diseases of the skin.