IL-6 Gene Expression as a Marker of Pathological State in Psoriasis and Psoriatic Arthritis

Соболев, В. В.; Денисова, Е. В.; Chebysheva, S.N.; Геппе, Н.А.; Korsunskaya, I. M.

doi:10.1007/s10517-022-05497-0

Cited by 18 publications

(13 citation statements)

References 12 publications

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“…The value of IL-6 as therapeutic target in several inflammatory and immune mediated has been postulated on psoriasis [ 53 ] and on atopic dermatitis, as demonstrated by data on Tocilizumab, a humanized monoclonal antibody directed against the IL-6 receptor, which in three case series demonstrated efficacy on pruritus and EASI index, in patients refractory to topical corticosteroid therapy and, in two cases, to cyclosporine [ 54 ].…”

Section: Discussionmentioning

confidence: 99%

Mesenchymal Stem Cells Profile in Adult Atopic Dermatitis and Effect of IL4-IL13 Inflammatory Pathway Inhibition In Vivo: Prospective Case-Control Study

Campanati

Orciani

Marani

et al. 2022

JCM

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Atopic dermatitis (AD) is an inflammatory disease that typically begins in childhood and may persist into adulthood, becoming a lifelong condition. The major inflammatory mediators of AD are known to be interleukin IL4 and IL13, so Dupilumab, which is able to inhibit both interleukins by blocking the shared IL4Rα subunit, has become an attractive option for treating AD. Mesenchymal stem cells (MSCs) are involved in the onset and development of AD by secreting specific interleukins. The aim of this study was to isolate MSCs from healthy controls (C-MSCs) and patients with AD before (AD-MSCs T0) and after 16 weeks of treatment with Dupilumab (AD-MSCs T16); to evaluate the expression mainly of IL4 and IL13 and of other inflammatory cytokines in C-MSCs, AD-MSCs at T0 and at T16; and to evaluate the efficacy of Dupilumab on MSCs immunobiology. C- and AD-MSCs (T0, T16) were isolated from skin specimens and characterized; the expression/secretion of IL4 and IL13 was evaluated using immuno-cytochemistry (ICC), indirect immune-fluorescence (IIF) and an ELISA test; secretion of IL2, IL4, IL5, IL6, IL10, IL12, IL13, IL17A, Interferon gamma (IFNγ), Tumor necrosis factor alpha (TNFα), Granulocyte Colony-Stimulating Factor (G-CSF), and Transforming Growth Factor beta1 (TGFβ1) were measured with ELISA. IL13 and IL6 were over-expressed, while IL4 was down-regulated in AD-MSCs at T0 compared to C-MSCs. IL6 and IL13 expression was restored after 16 weeks of Dupilumab treatment, while no significant effects on IL4 expression were noted. Finally, IL2, IL5, IL10, IL12, IL17A, INFγ, TNFα, G-CSF, and TGFβ1 were similarly secreted by C- and AD-MSCs. Although Dupilumab blocks the IL4Rα subunit shared by IL4 and IL13, it is evident that its real target is IL13, and its ability to target IL13 in MSCs reinforces the evidence, already known in differentiated cells, of the central role IL13 rather than IL4 in the development of AD. The inflammatory cascade in AD begins at the mesenchymal level, so an upstream therapeutic intervention, able to modify the immunobiology of atopic MSCs, could potentially change the natural history of the disease.

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Section: Discussionmentioning

confidence: 99%

Mesenchymal Stem Cells Profile in Adult Atopic Dermatitis and Effect of IL4-IL13 Inflammatory Pathway Inhibition In Vivo: Prospective Case-Control Study

Campanati

Orciani

Marani

et al. 2022

JCM

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“…Блокада TNF-α приводила к значительному снижению экспрессии TLR2 в моноцитах крови и синовиальной оболочке [14]. При этом неоднократно отмечалась гиперэкспрессия провоспалительных цитокинов, в т. ч. TNF-α [15], IL-6 [16][17][18][19], IL-17 [20,21], S100A8/9 [22,23], STAT3 [24], PPARγ [25][26][27], COMT [28], в иммунных клетках больных псориатическим артритом.…”

Section: Discussionunclassified

A potential inflammatory role of Toll-like receptor-2 in psoriatic arthritis

et al. 2023

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Introduction. Psoriatic arthritis is a chronic inflammatory disease that is characterized by cellular infiltration and production of pro-inflammatory cytokines and can be initiated by excessive activation of endosomal toll-like receptors (TLRs), particularly TLR2. Studying the TLR2 gene expression patterns can help choose a therapy for patients with psoriatic arthritis.Aim. To study the pattern of TLR2 gene expression in blood mononuclear cells of patients with psoriatic arthritis to assess its potential pro-inflammatory role.Materials and methods. Mononuclear cells were isolated from the peripheral blood of 31 patients with plaque psoriasis, 45 patients with psoriatic arthritis and 20 healthy controls. The expression level of the TNF gene was analysed using a real-time PCR method.Results and discussion. The comparative analysis of the expression levels of patients with psoriatic arthritis and healthy volunteers showed that the expression level of TNF in patients with psoriatic arthritis was 63 times higher than the expression level in healthy volunteers.Conclusions. A high level of TLR2 gene expression can indicate its role in the inflammatory process and become a marker of possible joint injury in patients with psoriasis.

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“…IL‐6 promotes keratinocyte proliferation, T lymphocyte differentiation and angiogenesis during psoriasis 41–44 . IL‐6 is highly expressed in the skin lesions and serum of patients with psoriasis, and the level of IL‐6 is correlated with psoriasis severity 45–49 . IL‐6 also predisposes patients with psoriasis to more frequent occurrences of depressive episodes, lipid abnormalities and cardiovascular comorbidities 50–52 .…”

Section: Discussionmentioning

confidence: 99%

“…[41][42][43][44] IL-6 is highly expressed in the skin lesions and serum of patients with psoriasis, and the level of IL-6 is correlated with psoriasis severity. [45][46][47][48][49] IL-6 also predisposes patients with psoriasis to more frequent occurrences of depressive episodes, lipid abnormalities and cardiovascular comorbidities. [50][51][52] Imiquimod increases the production of IL-6 in the adipose tissue of obese mice and higher IL-6 levels increase Th17 cell differentiation compared with those in normal mice.…”

Section: Discussionmentioning

confidence: 99%

Serine deficiency exacerbates psoriatic skin inflammation by regulating S‐adenosyl methionine‐dependentDNAmethylation andNF‐κBsignalling activation in keratinocytes

Meng,

Liu,

Yao

et al. 2023

Acad Dermatol Venereol

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BackgroundSerine metabolism is crucial for tumor oncogenesis and immune responses. S‐adenosyl methionine (SAM), a methyl donor, is typically derived from serine‐driven one‐carbon metabolism. However, the involvement of serine metabolism in psoriatic skin inflammation remains unclear.ObjectivesTo investigate the association between serine metabolism and psoriatic skin inflammation.MethodsClinical samples were collected from patients with psoriasis and the expression of serine biosynthesis enzymes was evaluated. The HaCaT human keratinocyte cell line was transfected with small interfering RNA (siRNA) of key enzyme or treated with inhibitors. RNA sequencing and DNA methylation assays were performed to elucidate the mechanisms underlying serine metabolism‐regulated psoriatic keratinocyte inflammation An imiquimod (IMQ)‐induced psoriasis mouse model was established to determine the effect of the SAM administration on psoriatic skin inflammation.ResultsThe expression of serine synthesis pathway enzymes, including the first rate‐limiting enzyme in serine biosynthesis, phosphoglycerate dehydrogenase (PHGDH), was downregulated in the epidermal lesions of patients with psoriasis compared with that in healthy controls. Suppressing PHGDH in keratinocytes promoted the production of proinflammatory cytokines and enrichment of psoriatic‐related signaling pathways, including the tumor necrosis factor‐alpha (TNF‐α) signaling pathway, interleukin (IL)‐17 signaling pathway, and NF‐κB signaling pathway. In particular, PHGDH inhibition markedly promoted the secretion of IL‐6 in keratinocytes with or without IL‐17A, IL‐22, IL‐1α, oncostatin M, and TNF‐α (mix) stimulation. Mechanistically, PHGDH inhibition upregulated the expression of IL‐6 by inhibiting SAM‐dependent DNA methylation at the promoter and increasing the binding of myocyte enhancer factor 2A. Furthermore, PHGDH inhibition increased the secretion of IL‐6 by increasing the activation of NF‐κB via SAM inhibition. SAM treatment effectively alleviated IMQ‐induced psoriasis‐like skin inflammation in mice.ConclusionsOur study revealed the crucial role of PHGDH in antagonizing psoriatic skin inflammation and indicated that targeting serine metabolism may represent a novel therapeutic strategy for treating psoriasis.

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IL-6 Gene Expression as a Marker of Pathological State in Psoriasis and Psoriatic Arthritis

Cited by 18 publications

References 12 publications

Mesenchymal Stem Cells Profile in Adult Atopic Dermatitis and Effect of IL4-IL13 Inflammatory Pathway Inhibition In Vivo: Prospective Case-Control Study

Mesenchymal Stem Cells Profile in Adult Atopic Dermatitis and Effect of IL4-IL13 Inflammatory Pathway Inhibition In Vivo: Prospective Case-Control Study

A potential inflammatory role of Toll-like receptor-2 in psoriatic arthritis

Serine deficiency exacerbates psoriatic skin inflammation by regulating S‐adenosyl methionine‐dependentDNAmethylation andNF‐κBsignalling activation in keratinocytes

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