A Nitric Oxide–Releasing Topical Medication as a Potential Treatment Option for Atopic Dermatitis through Antimicrobial and Anti-Inflammatory Activity

Guttman‐Yassky, Emma; Gallo, Richard L.; Pavel, Ana B.; Nakatsuji, Teruaki; Li, Randall; Zhang, N.; Messersmith, Elizabeth M; Maeda-Chubachi, Tomoko

doi:10.1016/j.jid.2020.04.013

Cited by 11 publications

(8 citation statements)

References 14 publications

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“…Likewise, inhibition of iNOS enhanced nickel-induced ear thickness by over 70% as compared to vehicle-treated ears [91]. Consistent with these findings in murine models, topical applications of an NO donor twice-daily for two weeks lowered eczema area and severity scores by 23% from the baseline, along with suppression of gene expression related to innate immunity (Th2, Th17/Th22, Th9, and Th1) pathways in humans with atopic dermatitis [90]. Taken together, these studies demonstrate the anti-inflammatory benefits of NO in cutaneous inflammation.…”

Section: Anti-inflammatory Effectssupporting

confidence: 68%

“…NO donor decreased expression levels of inflammationrelated genes [90] Nickel-induced inflammation in the mouse dermis Allergic inflammation was induced by the intradermal injection of nickel chloride. An iNOS inhibitor, L-NIL (100 μM), was co-administrated with nickel NOS inhibitor increased ear swelling [91] iNOS KO mice Inflammation caused by subcutaneous implantation iNOS KO mice exhibited increased neutrophil and macrophage infiltration and collagen deposition;…”

Section: Pro-inflammatory Effectsmentioning

confidence: 99%

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Regulatory Role of Nitric Oxide in Cutaneous Inflammation

et al. 2022

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Nitric oxide (NO), a signaling molecule, regulates biological functions in multiple organs/tissues, including the epidermis, where it impacts permeability barrier homeostasis, wound healing, and antimicrobial defense. In addition, NO participates in cutaneous inflammation, where it exhibits pro-inflammatory properties via the cyclooxygenase/prostaglandin pathway, migration of inflammatory cells, and cytokine production. Yet, NO can also inhibit cutaneous inflammation through inhibition of T cell proliferation and leukocyte migration/infiltration, enhancement of T cell apoptosis, as well as through down-regulation of cytokine production. Topical applications of NO-releasing products can alleviate atopic dermatitis in humans and in murine disease models. The underlying mechanisms of these discrepant effects of NO on cutaneous inflammation remain unknown. In this review, we briefly review the regulatory role of NO in cutaneous inflammation and its potential, underlying mechanisms.

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Section: Anti-inflammatory Effectssupporting

confidence: 68%

Section: Pro-inflammatory Effectsmentioning

confidence: 99%

Regulatory Role of Nitric Oxide in Cutaneous Inflammation

et al. 2022

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“…Thus, it cannot be concluded if the elevated NO is related to TSA/TSW or the underlying inflammatory skin condition. Finally, NO seems to exhibit both anti-or pro-inflammatory effects [60][61][62] depending on its concentration and microenvironment, with studies showing beneficial anti-inflammatory effects of topical NOreleasing compounds [62,63]. Further investigation into the relationship between NO levels, disease course and treatment will be helpful.…”

Section: Rebound Vasodilationmentioning

confidence: 99%

Steroid Phobia: Is There a Basis? A Review of Topical Steroid Safety, Addiction and Withdrawal

2021

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There is a growing concern amongst patients about topical corticosteroid (TCS) side effects, with increasing discussion of topical steroid addiction (TSA) and topical steroid withdrawal (TSW) particularly on social media platforms. However, the acceptance of TSA/TSW as a distinct condition remains controversial within the dermatological community. We conducted a literature search using PubMed, MEDLINE, Cochrane Library, Google Scholar, Embase and Web of Science to identify original articles addressing TSA/TSW. We described the definition and reported clinical features of TSA/TSW including its classification into erythemato-edematous and papulopustular subtype. To assess the validity of TSA/TSW, we summarised and objectively appraised the postulated mechanisms for this condition, including tachyphylaxis, dysregulation of glucocorticoid receptors, rebound vasodilation and impaired skin barrier leading to a cytokine cascade. Understanding the evidence including its limitations and uncertainties highlights areas for future research and helps medical practitioners better counsel and provide care to patients who may be experiencing or who have concerns about TSA/TSW.

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“…RNA-seq was also found to be superior in detecting low abundance transcripts in activated T-cells [6]. Benefiting from the improvement in throughput and the decrease of pricing of NGS, RNA-seq has been used in an increasing number of AD transcriptomics studies [7][8][9]. As a result, it is imperative to develop a new meta-analysis to include both data types and evaluate the AD gene signature from each technology, as well as combined technologies.…”

Section: Introductionmentioning

confidence: 99%

Meta-Analyzed Atopic Dermatitis Transcriptome (MAADT) is strongly correlated with disease activity, and consistent with therapeutic effects

Zhang

et al. 2022

Preprint

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Background: Atopic Dermatitis (AD) is a persistent inflammatory disease of the skin to which a few novel treatment options have recently become available. Multiple published datasets, from RNA sequencing (RNA-seq) and microarray experiments performed on lesional (LS) and non-lesional (NL) skin biopsies collected from AD patients, provide a useful resource to better define an AD gene signature and evaluate therapeutic effects. Methods: We evaluated 22 datasets using defined selection criteria and leave-one-out analysis and then carried out a meta-analysis (M-A) to combine 4 RNA-seq datasets and 5 microarray datasets to define a disease gene signature for AD skin tissue. We used this gene signature to evaluate its correlation to disease activity in published AD datasets, as well as the treatment effect of some of the existing and experimental therapies. Results: We report the AD gene signatures developed separately from the RNA-seq or the microarray datasets, as well as a gene signature from datasets combined across these two technologies; all 3 gene signatures showed a strong correlation to the disease activity score (SCORAD) - microarray: Pearson's rho = 0.651, p-value < 0.01, RNA-seq: rho = 0.640, p < 0.01, combined: rho = 0.649, p < 0.01. The gene signature improvement (GSI) of two existing effective therapies, Dupilumab and Cyclosporine, as well as that of other experimental treatments, is consistent with their reported cohort level efficacy from the associated clinical trials. Conclusions: The M-A derived AD gene signature provides an evolution of an important resource to correlate gene expression to disease activity and will be helpful for evaluating potential treatment effects for novel therapies.

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A Nitric Oxide–Releasing Topical Medication as a Potential Treatment Option for Atopic Dermatitis through Antimicrobial and Anti-Inflammatory Activity

Cited by 11 publications

References 14 publications

Regulatory Role of Nitric Oxide in Cutaneous Inflammation

Regulatory Role of Nitric Oxide in Cutaneous Inflammation

Steroid Phobia: Is There a Basis? A Review of Topical Steroid Safety, Addiction and Withdrawal

Meta-Analyzed Atopic Dermatitis Transcriptome (MAADT) is strongly correlated with disease activity, and consistent with therapeutic effects

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