Emerging role of immune cell network in autoimmune skin disorders: An update on pemphigus, vitiligo and psoriasis

Das, Dayasagar; Akhtar, Shamima; Kurra, Santosh; Gupta, Somesh; Sharma, Alpana

doi:10.1016/j.cytogfr.2019.01.001

Cited by 64 publications

(55 citation statements)

References 96 publications

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“…The results of GO enrichment analysis indicated that immune response and inflammatory response play a significant role in VKH disease, which confirms earlier studies in this field (19)(20)(21)(22)(23). There still are many mediators related to these pathways, which have not been reported to be associated with VKH disease.…”

Section: Discussionsupporting

confidence: 83%

Integrated Analysis of Key Pathways and Drug Targets Associated With Vogt-Koyanagi-Harada Disease

et al. 2020

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BackgroundVogt-Koyanagi-Harada (VKH) disease is a complex disease associated with multiple molecular immunological mechanisms. As the underlying mechanism for VKH disease is unclear, we hope to utilize an integrated analysis of key pathways and drug targets to develop novel therapeutic strategies.MethodsCandidate genes and proteins involved in VKH disease were identified through text-mining in the PubMed database. The GO and KEGG pathway analyses were used to examine the biological functions of the involved pathways associated with this disease. Molecule-related drugs were predicted through Drug-Gene Interaction Database (DGIdb) analysis.ResultsA total of 48 genes and 54 proteins were associated with VKH disease. Forty-two significantly altered pathways were identified through pathway analysis and were mainly related to immune and inflammatory responses. The top five of significantly altered pathways were termed as “inflammatory bowel disease,” “cytokine-cytokine receptor interaction,” “allograft rejection,” “antigen processing,” and “presentation and Herpes simplex infection” in the KEGG database. IFN-γ and IL-6 were identified as the key genes through network analysis. The DGIdb analysis predicted 48 medicines as possible drugs for VKH disease, among which Interferon Alfa-2B was co-associated both with IFN-γ and IL-6.ConclusionsIn this study, systematic analyses were utilized to detect key pathways and drug targets in VKH disease via bioinformatics analysis. IFN-γ and IL-6 were identified as the key mediators and possible drug targets in VKH disease. Interferon Alfa-2B was predicted to be a potentially effective drug for VKH disease treatment by targeting IFN-γ and IL-6, which warrants further experimental and clinical investigations.

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Section: Discussionsupporting

confidence: 83%

Integrated Analysis of Key Pathways and Drug Targets Associated With Vogt-Koyanagi-Harada Disease

et al. 2020

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“…Its pathogenesis involves hyperkeratosis of the epidermis, characterized by inflammatory skin infiltrates, epidermal hypertrophy, and dysregulated keratinocytes proliferation, differentiation, and desquamation [1]. It is believed that the pathogenesis of psoriasis is the result of impaired immunity, possessing a genetic component linked to immune genes and their encoded pathways [2]. In recent years, the dysregulation of these genes, including TNF-α and IL-23, has been shown to participate in the development of psoriasis [3].…”

Section: Introductionmentioning

confidence: 99%

Cannabidiol Effects on Phospholipid Metabolism in Keratinocytes from Patients with Psoriasis Vulgaris

Jarocka-Karpowicz

Biernacki

Wroński³

et al. 2020

Biomolecules

101

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Psoriasis is a chronic inflammatory skin disease characterized by dysregulated keratinocyte differentiation, but oxidative stress also plays an important role in the pathogenesis of this disease. Here, we examined the effect of cannabidiol (CBD), a phytocannabinoid with antioxidant and anti-inflammatory properties, on the redox balance and phospholipid metabolism in UVA/UVB-irradiated keratinocytes isolated from the skin of psoriatic patients or healthy volunteers. CBD accumulates mainly in membrane keratinocytes, especially from patients with psoriasis. This phytocannabinoid reduces the redox imbalance observed in the UV-irradiated keratinocytes of healthy subjects. It does so by decreasing reactive oxygen species (ROS) generation, increasing the Trx-dependent system efficiency, and increasing vitamin A and E levels. Consequently, a reduction in lipid peroxidation products, such as 8-isoprostanes and 4-hydroxynonenal, was also observed. Moreover, CBD modifies redox balance and lipid peroxidation in psoriatic patient keratinocytes following UV-irradiation. Interestingly, these changes are largely in the opposite direction to the case of keratinocytes from healthy subjects. CBD also regulates metabolic changes by modulating the endocannabinoid system that is disturbed by psoriasis development and UV irradiation. We observed a decrease in anandamide level in the UV-irradiated keratinocytes of healthy controls following CBD treatment, while in keratinocytes from patients treated with CBD, anandamide level was increased. However, the level of palmitoylethanolamide (PEA) was decreased in both groups treated with CBD. We further demonstrate that CBD increases CB1 receptor expression, primarily in the keratinocytes of patients, and increases CB2 receptor expression in both the psoriatic and control groups. However, CBD decreases CB2 receptor expression in UV-irradiated keratinocytes taken from patients. The UV- and psoriasis-induced activity of transmembrane transporters (Multidrug-Resistance (MDR) and breast cancer resistance protein (BCRP)) is normalized after CBD treatment. We conclude that CBD partially reduces oxidative stress in the keratinocytes of healthy individuals, while showing a tendency to increase the oxidative and inflammatory state in the keratinocytes of patients with psoriasis, especially following UV-irradiation.

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“…Psoriasis is a T-cell-mediated immune disease characterized by increased keratinocyte proliferation leading to the formation of well-demarcated erythematous plaques with scaling. 2 CD and ulcerative colitis (UC) are parts of the spectrum of IBD. All three conditions result from immune dysregulation due to genetic predisposition and environmental assaults.…”

Section: Discussionmentioning

confidence: 99%

Asymptomatic Crohn’s disease identified in a patient being treated with secukinumab: A case report

Haidari

Al-Naqshabandi

Ahn

et al. 2019

SAGE Open Medical Case Reports

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IL-17 antagonism is among the most potent treatments for psoriasis. Generally safe, new onset and exacerbations of inflammatory bowel disease may occur in association with IL-17 therapy. We describe a patient with long-standing history of psoriasis and psoriatic arthritis in whom asymptomatic Crohn’s disease was identified during treatment with secukinumab. The patient underwent an elective colonoscopy for colorectal cancer screening which revealed inflammation and multiple ulcers in the terminal ileum suggestive of Crohn’s disease. While the patient did not have any gastrointestinal symptoms, he was diagnosed as having asymptomatic Crohn’s disease. Given the association of inflammatory bowel disease with secukinumab treatment, secukinumab was discontinued. Although in this patient, Crohn’s disease was identified during treatment with secukinumab, a direct causal relationship cannot be assumed. Medications that are effective for both psoriasis and inflammatory bowel disease may be a good choice in patients with psoriasis who have comorbid Crohn’s disease or develop inflammatory bowel disease during treatment with another biologic.

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Emerging role of immune cell network in autoimmune skin disorders: An update on pemphigus, vitiligo and psoriasis

Cited by 64 publications

References 96 publications

Integrated Analysis of Key Pathways and Drug Targets Associated With Vogt-Koyanagi-Harada Disease

Integrated Analysis of Key Pathways and Drug Targets Associated With Vogt-Koyanagi-Harada Disease

Cannabidiol Effects on Phospholipid Metabolism in Keratinocytes from Patients with Psoriasis Vulgaris

Asymptomatic Crohn’s disease identified in a patient being treated with secukinumab: A case report

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