Targeting interferons as a strategy for systemic sclerosis treatment

Ciechomska, Marzena; Skalska, Urszula

doi:10.1016/j.imlet.2017.10.011

Cited by 21 publications

(13 citation statements)

References 134 publications

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“…Anifrolumab is a monoclonal antibody that suppresses type I IFN production via binding to the type I IFN receptor and is currently used in clinical trials. Indeed, anifrolumab has been developed to treat autoimmune diseases and is used in clinical trials phase III to treat SLE, phase II to treat lupus nephritis, and phase I to treat SSc [8‐10]. These results suggest that monocytes are associated with IFN‐mediated SSc pathogenesis.…”

Section: Introductionmentioning

confidence: 99%

Global miRNA and mRNA expression profiles identify miRNA‐26a‐2‐3p‐dependent repression of IFN signature in systemic sclerosis human monocytes

et al. 2020

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Dysregulation in type I IFN and IFN-stimulated genes (ISGs) induced by monocytes is one of the key features of systemic sclerosis (SSc) pathogenesis. Abnormalities in microRNA (miRNA) expression are related to excessive IFN production, however the role of miRNA remains largely elusive in SSc monocytes. This study explores global miRNA-mRNA profiling of SSc monocytes and functional attenuation of IFN and ISGs by specific miR-NAs. Global sequencing of mRNA (mRNA-seq) and miRNA (miRNA-seq) samples were performed simultaneously on healthy controls and SSc monocytes. Following computational analysis, selected miRNAs-mRNA candidates were validated, correlated with clinical parameters, and tested by functional assays. Transcriptomics data and qPCR analysis confirmed IFN signature in SSc but not in rheumatoid arthritis monocytes. Based on miRNA-seq analysis, five miRNAs were selected for further validation. Only the expression patterns of miRNA-26a-2-3p and miRNA-485-3p were confirmed and negatively correlated with clinical parameters. Exogenous delivery of miRNA-26a-2-3p to TLR-stimulated monocytic THP-1 cells specifically inhibited ISGs but not inflammasome activity in functional assays. In conclusion, our miRNA-mRNA co-sequencing and functional analysis identify miRNA-26a-2-3p as a new candidate, which is predicated to negatively regulate ISGs. This implies that reduced expression of miRNA-26a-2-3 may be involved in pathogenic IFN signature in SSc monocytes.

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Section: Introductionmentioning

confidence: 99%

Global miRNA and mRNA expression profiles identify miRNA‐26a‐2‐3p‐dependent repression of IFN signature in systemic sclerosis human monocytes

et al. 2020

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“…INF‐γ is a powerful immunomodulatory cytokine acting on specific cell surface receptors named IFNGR1 and INFGR2, which are associated with JAK1 and JAK2 kinases pathways . INF‐γ is induced by exogenous and endogenous stimuli, with important role in several diseases, such as systemic lupus erythematosus, rheumatoid arthritis, dermatomyositis, systemic sclerosis, and skin fibrosis . Since hydrocortisone acts as anti‐ inflammatory drug, including a suppression of INF‐γ production, HCT effects on INF‐γ production by both non‐stimulated and LPS‐stimulated conditions here observed were completely expected.…”

Section: Discussionmentioning

confidence: 59%

Sterol‐standardized phytopharmaceutical from ground cherry: Corticoid‐like properties on human keratinocytes and fibroblasts and its effects in a randomized double‐blind placebo‐controlled clinical trial

Pereda

Dieamant

Nogueira

et al. 2018

J of Cosmetic Dermatology

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Background: Topical corticosteroids have been the most commonly prescribed drugs to treat skin inflammation, but their uses can lead to several adverse effects. Nowadays, new pharmacological strategies have been evaluated to improve dermatologic efficacy and reduce adverse effects, including natural products. Objectives:The aim of this study was to evaluate and compare the effects of a plant sterol standardized supercritical CO 2 phytopharmaceutical of Physalis angulata L. with hydrocortisone on the immune and inflammatory mediators, and skin repair components production. Moreover, we studied effects of both products on the skin microcirculation and temperature in a double-blind placebo-controlled clinical trial.Methods: Both products were evaluated on the immune (IL-6, IL-10, INF-γ, TNF-α, and IL-1α), inflammatory (COX-2, LOX, PLA 2 , PGE 2 , LTB 4 , histamine, and NF-κB), and repair components (TGF-β, GM-CSF, collagen, and GAG) production on human keratinocytes and fibroblast in non-stimulated and LPS-stimulated conditions. Indeed, in a randomized double-blind placebo-controlled clinical trial, we evaluated the effects of the both creams on the skin microcirculation and temperature using laser Doppler and infrared thermometer, respectively. Results:Physalis angulata acted on the skin, modulating immune status and inflammatory response producing corticoid-like effects, but different of hydrocortisone, increased skin repair factors. The effects of phytopharmaceutical cream in the clinical trial promoted a better reduction in skin microcirculation and temperature than hydrocortisone.Conclusions: Taken together, the results indicate that sterol standardized CO 2 supercritical preparation of P angulata is a new and innovative phytopharmaceutical with multiple pharmacological effects potentially useful as human skin protective product, particularly against cutaneous inflammatory disorders.

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“…The consequences of increased type I IFN expression in SSc are diverse and affect immune and endothelial cell function as well as fibroblasts. These effects have been extensively reviewed by Ciechomska and Skalska [38] and are outlined below.…”

Section: Etiopathogenesis Of Systemic Sclerosis and Therapeutic Tamentioning

confidence: 99%

“…IFN type I effects on immune cells include increased monocyte activation, as well as increased differentiation, survival, proliferation, and activation of T, B, and dendritic cells [10, 36, 38–41]. Moreover, Kim et al showed that serum of SSc patients containing anti-topoisomerase I antibodies induces the production of interferon-alpha by PBMCs cocultured with nuclear extracts.…”

Section: Etiopathogenesis Of Systemic Sclerosis and Therapeutic Tamentioning

confidence: 99%

“…Interferons are pleiotropic cytokines that play a fundamental role as factors responsible for the immune response, mainly in bacterial and viral infections; however, they have also been strongly associated with the pathogenesis of SSc because of their notorious correlation with skin thickness and disease activity when found in elevated levels in patients' blood and sera [38]. Consequently, several clinical trials have been executed in order to test the potential benefits on directed anti-IFN treatments, as follows:…”

Section: Etiopathogenesis Of Systemic Sclerosis and Therapeutic Tamentioning

confidence: 99%

See 1 more Smart Citation

Systemic Sclerosis Pathogenesis and Emerging Therapies, beyond the Fibroblast

Sierra-Sepúlveda

Esquinca-González

Suárez

et al. 2019

BioMed Research International

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Systemic sclerosis (SSc) is a complex rheumatologic autoimmune disease in which inflammation, fibrosis, and vasculopathy share several pathogenic pathways that lead to skin and internal organ damage. Recent findings regarding the participation and interaction of the innate and acquired immune system have led to a better understanding of the pathogenesis of the disease and to the identification of new therapeutic targets, many of which have been tested in preclinical and clinical trials with varying results. In this manuscript, we review the state of the art of the pathogenesis of this disease and discuss the main therapeutic targets related to each pathogenic mechanism that have been discovered so far.

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Targeting interferons as a strategy for systemic sclerosis treatment

Cited by 21 publications

References 134 publications

Global miRNA and mRNA expression profiles identify miRNA‐26a‐2‐3p‐dependent repression of IFN signature in systemic sclerosis human monocytes

Global miRNA and mRNA expression profiles identify miRNA‐26a‐2‐3p‐dependent repression of IFN signature in systemic sclerosis human monocytes

Sterol‐standardized phytopharmaceutical from ground cherry: Corticoid‐like properties on human keratinocytes and fibroblasts and its effects in a randomized double‐blind placebo‐controlled clinical trial

Systemic Sclerosis Pathogenesis and Emerging Therapies, beyond the Fibroblast

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