Investigation of the Role of Interleukin 6 in Vitiligo Pathogenesis

Singh, Mala; Jadeja, Shahnawaz D.; Vaishnav, Jayvadan; Mansuri, Mohmmad Shoab; Shah, Chandni; Mayatra, Jay; Shah, Atul A.

doi:10.1080/08820139.2020.1813756

Cited by 19 publications

(13 citation statements)

References 65 publications

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“…Higher IFN-c and IL-6 levels have been observed in the blood and skin of vitiligo patients [47][48][49][50] and are indexes for vitiligo diagnosis. [46,51]. CWT showed a more potent effect than BC in the guinea pig model, unlike in the mouse 14 Evidence-Based Complementary and Alternative Medicine model.…”

Section: Discussionmentioning

confidence: 91%

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Effects of a Traditional Caraway Formulation on Experimental Models of Vitiligo and Mechanisms of Melanogenesis

Abuduaini

Lü

Zang

et al. 2021

Evidence-Based Complementary and Alternative Medicine

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Background. Kursi Karwiya or caraway tablet (CWT), a traditional medicine formula, is widely used in Xinjiang, China, for treating vitiligo, a common autoimmune disease for which there is currently no satisfactory cure. Clinical interventions include pharmacological treatment with psoralens, often in conjunction with UVA radiation, but toxic side effects limit this application. Studies on the activities and mechanisms of CWT are scarce. Objective. To investigate the in vitro and in vivo effects of CWT in B16 cell line and in animal models of vitiligo, further exploring its mechanisms of regulating melanogenesis. Methods. Effects of CWT on melanin synthesis in B16 cells and mushroom tyrosinase activity were investigated in vitro. The signaling pathway of melanogenesis in murine B16 melanoma cells was examined by Western blotting. Two different animal models were used, vitiligo induced by hydroquinone in the mouse model and by hydrogen peroxide in the guinea pig model. Relevant biochemical parameters in blood and skin tissue were measured, and visual inspection, histopathology, and immunohistochemical analysis of treated areas were carried out. Results. CWT produced changes in biochemical parameters including TYR, MDA, MAO, AChE, IL-6, INF-α, β-EP, and cAMP in blood and/or skin tissue and in regulating melanogenesis. After treatment with CTW, skin color, melanin containing hair follicles, and expression of TYR, TRP-1, and TRP-2 in the skin of animals were significantly affected. Conclusions. CWT alleviated many of detrimental effects in both models of vitiligo. Tyrosinase activity and melanin content in B16 cells were increased, at least in part, via activation of the PKA p38 MAPK signaling pathways. Our results show that CWT produces beneficial effects on parameters of vitiligo and is worthy of further investigation for use in this distressing autoimmune disorder which currently has no effective cure.

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Section: Discussionmentioning

confidence: 91%

“…Levels of interleukin-6 (IL-6), a proinflammatory cytokine and key factor in the pathogenesis of autoimmune diseases, have been reported to be elevated in vitiligo lesions [46]. Higher IFN-c and IL-6 levels have been observed in the blood and skin of vitiligo patients [47][48][49][50] and are indexes for vitiligo diagnosis.…”

Section: Discussionmentioning

confidence: 99%

Effects of a Traditional Caraway Formulation on Experimental Models of Vitiligo and Mechanisms of Melanogenesis

Abuduaini

Lü

Zang

et al. 2021

Evidence-Based Complementary and Alternative Medicine

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“…Therefore, IL-6 might have a role in the activation of immune responses following oxidative injuries in vitiligo [ 55 ]. Moreover, a specific IL-6 polymorphism, IL6-5 72 G/C, has been proposed to be associated with vitiligo susceptibility in the Gujarat population [ 56 ].…”

Section: Vitiligo Pathogenesis: Ab Origine Development From Gene To Cellular Dynamicsmentioning

confidence: 99%

Role of Cytokines in Vitiligo: Pathogenesis and Possible Targets for Old and New Treatments

Custurone

Bartolomeo

Irrera

et al. 2021

IJMS

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Vitiligo is a chronic autoimmune dermatosis of which the pathogenesis remains scarcely known. A wide variety of clinical studies have been proposed to investigate the immune mediators which have shown the most recurrency. However, such trials have produced controversial results. The aim of this review is to summarize the main factors involved in the pathogenesis of vitiligo, the latest findings regarding the cytokines involved and to evaluate the treatments based on the use of biological drugs in order to stop disease progression and achieve repigmentation. According to the results, the most recurrent studies dealt with inhibitors of IFN-gamma and TNF-alpha. It is possible that, given the great deal of cytokines involved in the lesion formation process of vitiligo, other biologics could be developed in the future to be used as adjuvants and/or to entirely replace the treatments that have proven to be unsatisfactory so far.

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“…Melanocytes exposed to monobenzone activate the UPR and increase expression of UPR‐regulated cytokines interleukin‐6 and interleukin‐8 (Toosi et al., 2012). These cytokines are expressed at high levels in skin from patients with vitiligo (Singh et al., 2020), suggesting sustained UPR activation. In addition, polymorphisms of the UPR‐related genes XBP1 and UVRAG have been found to associate with risk of developing vitiligo (Jeong et al., 2010; Ren et al., 2009).…”

Section: The Upr/isr In Disease Pathologymentioning

confidence: 99%

The unfolded protein and integrated stress response in melanoma and vitiligo

Manga

Choudhury

2020

Pigment Cell Melanoma Res

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Epidermal melanocytes are constantly exposed to environmental stressors such as ultraviolet light (UV) and chemotoxins. Several evolutionarily conversed survival mechanisms are deployed to ensure melanocyte recovery after damage including the unfolded protein response (UPR) and integrated stress response (ISR). The UPR/ISR promote restoration of homeostasis, by modulating transcription and translation as well as activating nuclear factor erythroid 2‐related factor 2 (NRF2)‐mediated antioxidant activity. If repair fails, the UPR/ISR either stimulate cell death, or adaptation that can lead to survival of damaged cells and promote disease. For example, the UPR/ISR may support melanomagenesis by allowing UV‐damaged, mutated cells to survive and adapt to a hostile tumor microenvironment that subjects cells to hypoxia, nutrient deprivation, and sub‐optimal pH. The UPR and ISR can also promote transcriptional changes that support tumor growth and/or metastasis. Furthermore, these pathways may also underlie acquisition of chemoresistance and modulation of protein expression that alters the efficacy of immunotherapies. UPR activation has also been implicated in the pathogenesis of vitiligo and may promote increased expression of chemokines such as interleukin 6 and interleukin 8 that trigger an autoimmune response against melanocytes. We herein review the potential roles of the UPR/ISR in the etiology of melanoma and vitiligo.

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Investigation of the Role of Interleukin 6 in Vitiligo Pathogenesis

Cited by 19 publications

References 65 publications

Effects of a Traditional Caraway Formulation on Experimental Models of Vitiligo and Mechanisms of Melanogenesis

Effects of a Traditional Caraway Formulation on Experimental Models of Vitiligo and Mechanisms of Melanogenesis

Role of Cytokines in Vitiligo: Pathogenesis and Possible Targets for Old and New Treatments

The unfolded protein and integrated stress response in melanoma and vitiligo

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