| 2291. |
- Sonesson, Andreas, et al.
(författare)
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Sensitization to Skin-associated Microorganisms in Adult Patients with Atopic Dermatitis is of Importance for Disease Severity.
- 2013
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Ingår i: Acta Dermato-Venereologica. - : Medical Journals Sweden AB. - 1651-2057 .- 0001-5555. ; 93:3, s. 340-345
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Tidskriftsartikel (refereegranskat)abstract
- Atopic dermatitis (AD) is a chronic inflammatory skin disease. Environmental and genetic factors, as well as microbial products from yeasts and bacteria, play a role in triggering the disease. A cohort of 619 adult patients with AD was screened for severity of AD, sensitization to Malassezia sympodialis, Candida albicans, Staphylococcus aureus enterotoxins and Dermatophagoides pteronyssinus. Serum levels of interleukin (IL)-18 were measured. Immunoglobulin E (IgE) sensitization to the combination of both yeast and mite antigens was found to be associated with more severe disease and higher levels of total IgE. AD patients with IgE sensitization to several microbial antigens had more severe disease than those with no IgE sensitization to microbial antigens. Sera from patients with IgE-associated AD showed higher levels of IL-18. Skin-associated microorganisms are exogenous factors triggering IgE-response and severity of AD. These findings are clinically important, and sensitization to these organisms should be assessed and considered in treatment strategies.
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| 2292. |
- Sonesson, Andreas, et al.
(författare)
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Thymic stromal lymphopoietin exerts antimicrobial activities
- 2011
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Ingår i: Experimental dermatology. - : Wiley. - 0906-6705 .- 1600-0625. ; 20:12, s. 1004-1010
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Tidskriftsartikel (refereegranskat)abstract
- Thymic stromal lymphopoietin (TSLP) is an interleukin-7-like cytokine expressed by epithelial cells and reported to be involved in allergic diseases and atopic eczema. The presence of several predicted a-helical regions in TSPL, a structure characterizing many classical antimicrobial peptides (AMPs), prompted us to investigate whether TSLP exerts antimicrobial activities. Recombinant human TSLP exerted antimicrobial activity, particularly against Gram-negative bacteria. Using synthetic overlapping peptide 20-mers of TSLP, it was demonstrated that the antimicrobial effect is primarily mediated by the C-terminal region of the protein. MKK34 (MKKRRKRKVTTNKCLEQVSQLQGLWRRFNRPLLK), a peptide spanning a C-terminal a-helical region in TSLP, showed potent antimicrobial activities, in physiological salt conditions and in the presence of human plasma. Fluorescent studies of peptide-treated bacteria, electron microscopy and liposome leakage models showed that MKK34 exerted membrane-disrupting effects comparable to those of the classical AMP LL-37. Moreover, TSLP was degraded into multiple fragments by staphylococcal V8 proteinase. One major antimicrobial degradation fragment was found to encompass the C-terminal antimicrobial region defined by the MKK34 peptide. We here describe a novel antimicrobial role for TSLP. The antimicrobial activity is primarily mediated by the C-terminal part of the protein. In combination with the previously known cytokine function of TSLP, our result indicates dual functions of the molecule and a previously unknown role in host defense.
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| 2293. |
- Sonesson, Björn C, et al.
(författare)
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UVB-induced inflammation gives increased d-dopachrome tautomerase activity in blister fluid which correlates with macrophage migration inhibitory factor.
- 2003
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Ingår i: Experimental Dermatology. - : Wiley. - 0906-6705. ; 12:3, s. 278-282
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Tidskriftsartikel (refereegranskat)abstract
- UVB light was used to induce an experimental inflammation in normal human skin in order to investigate its correlation with the activity of the newly described enzyme d-dopachrome tautomerase (DDT) in the fluid of experimental blisters. Macrophage migration inhibitory factor (MIF) activity was determined as a closely related marker of inflammation. DDT and MIF activities were demonstrated in blister fluids in all 10 healthy subjects. All but one of these subjects showed increased activity of DDT and MIF after three minimal erythemal doses (MED) of UVB. The mean activity of DDT increased approximately twofold and the mean activity of MIF also increased twofold after UVB in our experimental model. We found a strong correlation between DDT and MIF activities. The presence of DDT in epidermis and its increase at UV irradiation was confirmed by immunohistochemical studies. In this study, DDT is for the first time demonstrated in the skin. It is also the first time DDT can be related to inflammation, and its covariation with MIF strengthens this observation.
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| 2294. |
- Sonkoly, Enikö, et al.
(författare)
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Guselkumab in Patients with Scalp Psoriasis : A post hoc Analysis of the VOYAGE 2 Phase III Randomized Clinical Trial
- 2024
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Ingår i: Acta Dermato-Venereologica. - : Acta Dermato-Venereologica. - 0001-5555 .- 1651-2057. ; 104
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Tidskriftsartikel (refereegranskat)abstract
- Scalp psoriasis affects approximately 80% of patients with psoriasis and can negatively impact their quality of life. This post hoc analysis of the VOYAGE 2 Phase III randomized clinical trial evaluated scalp response to guselkumab treatment and its association with skin response and patient -reported outcomes. The study included patients with moderate -to -severe plaque psoriasis and baseline scalp psoriasis who were initially randomized to receive guselkumab. Patients were divided into 3 groups based on their achievement of a Psoriasis Area and Severity Index 90 response at week 28: responder continuation, non -responder continuation and responder withdrawal. In all 3 groups, mean Psoriasis Area and Severity Index head and scalpspecific Investigator's Global Assessment scores improved through week 28. In the responder withdrawal group, these scores worsened after treatment withdrawal at week 28, but remained stable through week 48 in both continuation groups. Trends in Dermatology Life Quality Index and Psoriasis Symptoms and Signs Diary itch scores mirrored those of mean scalp -specific Investigator's Global Assessment scores through week 48. Within -subject correlations were 0.83 between scalp -specific Investigator's Global Assessment and Psoriasis Area and Severity Index head scores and 0.78 between scalp -specific Investigator's Global Assessment and Psoriasis Symptoms and Signs Diary itch scores. Through week 252, Psoriasis Area and Severity Index head scores remained stable in the responder continuation group, improved in the non -responder continuation group and rapidly improved by week 84 in the responder withdrawal group after retreatment.
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| 2295. |
- Sonkoly, Eniko, et al.
(författare)
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Identification and characterization of a novel, psoriasis susceptibility-related noncoding RNA gene, PRINS.
- 2005
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Ingår i: Journal of Biological Chemistry. - 0021-9258 .- 1083-351X. ; 280:25, s. 24159-67
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Tidskriftsartikel (refereegranskat)abstract
- To identify genetic factors contributing to psoriasis susceptibility, gene expression profiles of uninvolved epidermis from psoriatic patients and epidermis from healthy individuals were compared. Besides already characterized genes, we identified a cDNA with yet unknown functions, which we further characterized and named PRINS (Psoriasis susceptibility-related RNA Gene Induced by Stress). In silico structural and homology studies suggested that PRINS may function as a noncoding RNA. PRINS harbors two Alu elements, it is transcribed by RNA polymerase II, and it is expressed at different levels in various human tissues. Real time reverse transcription-PCR analysis showed that PRINS was expressed higher in the uninvolved epidermis of psoriatic patients compared with both psoriatic lesional and healthy epidermis, suggesting a role for PRINS in psoriasis susceptibility. PRINS is regulated by the proliferation and differentiation state of keratinocytes. Treatment with T-lymphokines, known to precipitate psoriatic symptoms, decreased PRINS expression in the uninvolved psoriatic but not in healthy epidermis. Real time reverse transcription-PCR analysis showed that stress signals such as ultraviolet-B irradiation, viral infection (herpes simplex virus), and translational inhibition increased the RNA level of PRINS. Gene-specific silencing of PRINS by RNA interference revealed that down-regulation of PRINS impairs cell viability after serum starvation but not under normal serum conditions. Our findings suggest that PRINS functions as a noncoding regulatory RNA, playing a protective role in cells exposed to stress. Furthermore, elevated PRINS expression in the epidermis may contribute to psoriasis susceptibility.
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| 2296. |
- Sonkoly, Eniko, et al.
(författare)
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IL-31 : a new link between T cells and pruritus in atopic skin inflammation.
- 2006
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Ingår i: Journal of Allergy and Clinical Immunology. - : Elsevier BV. - 0091-6749 .- 1097-6825. ; 117:2, s. 411-7
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: IL-31 is a novel T-cell-derived cytokine that induces severe pruritus and dermatitis in transgenic mice, and signals through a heterodimeric receptor composed of IL-31 receptor A and oncostatin M receptor.OBJECTIVE: To investigate the role of human IL-31 in pruritic and nonpruritic inflammatory skin diseases.METHODS: The expression of IL-31 was analyzed by quantitative real-time PCR in skin samples of healthy individuals and patients with chronic inflammatory skin diseases. Moreover, IL-31 expression was analyzed in nonlesional skin of atopic dermatitis patients after allergen or superantigen exposure, as well as in stimulated leukocytes. The tissue distribution of the IL-31 receptor heterodimer was investigated by DNA microarray analysis.RESULTS: IL-31 was significantly overexpressed in pruritic atopic compared with nonpruritic psoriatic skin inflammation. Highest IL-31 levels were detected in prurigo nodularis, one of the most pruritic forms of chronic skin inflammation. In vivo, staphylococcal superantigen rapidly induced IL-31 expression in atopic individuals. In vitro, staphylococcal enterotoxin B but not viruses or T(H)1 and T(H)2 cytokines induced IL-31 in leukocytes. In patients with atopic dermatitis, activated leukocytes expressed significantly higher IL-31 levels compared with control subjects. IL-31 receptor A showed most abundant expression in dorsal root ganglia representing the site where the cell bodies of cutaneous sensory neurons reside.CONCLUSION: Our findings provide a new link among staphylococcal colonization, subsequent T-cell recruitment/activation, and pruritus induction in patients with atopic dermatitis. Taken together, these findings show that IL-31 may represent a novel target for antipruritic drug development.
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| 2297. |
- Sonkoly, E, et al.
(författare)
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MicroRNAs : novel regulators in skin inflammation.
- 2008
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Ingår i: Clincal and Experimental Dermatology. - : Oxford University Press (OUP). - 0307-6938 .- 1365-2230. ; 33:3, s. 312-5
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Tidskriftsartikel (refereegranskat)abstract
- Compelling evidence indicates that microRNAs (miRNAs), short, non-protein coding RNAs, are critical for the development and survival of multicellular organisms. Recently, miRNAs were implicated in the pathogenesis of psoriasis and atopic eczema (AE), the two most common chronic inflammatory disorders in skin. In particular, miR-203, the first skin-specific miRNA, showing an intriguing expression profile being confined to skin epithelium, is specifically overexpressed in psoriasis. MiR-146a, another miRNA showing specific upregulation in psoriasis, is involved in the regulation of innate immune responses and the tumour necrosis factor (TNF)-alpha pathway. Interestingly, miR-125b, another miRNA involved in the TNF-alpha pathway, is also deregulated in psoriasis and AE. As skin inflammation may serve as a model for chronic inflammatory disorders, it is likely that miRNAs involved in skin inflammation will eventually emerge in other inflammatory or autoimmune disorders, and some of these may become disease markers and therapeutic targets. In this review we present an overview of what is currently known about the roles of miRNAs in chronic inflammatory skin disorders.
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| 2298. |
- Sonkoly, Enikö, et al.
(författare)
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MicroRNAs : novel regulators involved in the pathogenesis of psoriasis?
- 2007
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Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 2:7
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Tidskriftsartikel (refereegranskat)abstract
- MicroRNAs are a recently discovered class of posttranscriptional regulators of gene expression with critical functions in health and disease. Psoriasis is the most prevalent chronic inflammatory skin disease in adults, with a substantial negative impact on the patients' quality of life. Here we show for the first time that psoriasis-affected skin has a specific microRNA expression profile when compared with healthy human skin or with another chronic inflammatory skin disease, atopic eczema. Among the psoriasis-specific microRNAs, we identified leukocyte-derived microRNAs and one keratinocyte-derived microRNA, miR-203. In a panel of 21 different human organs and tissues, miR-203 showed a highly skin-specific expression profile. Among the cellular constituents of the skin, it was exclusively expressed by keratinocytes. The up-regulation of miR-203 in psoriatic plaques was concurrent with the down-regulation of an evolutionary conserved target of miR-203, suppressor of cytokine signaling 3 (SOCS-3), which is involved in inflammatory responses and keratinocyte functions. Our results suggest that microRNA deregulation is involved in the pathogenesis of psoriasis and contributes to the dysfunction of the cross talk between resident and infiltrating cells. Taken together, a new layer of regulatory mechanisms is involved in the pathogenesis of chronic inflammatory skin diseases.
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| 2299. |
- Sonkoly, Enikö, et al.
(författare)
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MiR-155 is overexpressed in patients with atopic dermatitis and modulates T-cell proliferative responses by targeting cytotoxic T lymphocyte-associated antigen 4.
- 2010
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Ingår i: Journal of Allergy and Clinical Immunology. - : Elsevier BV. - 0091-6749 .- 1097-6825. ; 126:3, s. 581-9.e1
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: MicroRNAs (miRNAs) are short noncoding RNAs that suppress gene expression at the posttranscriptional level. Atopic dermatitis is a common chronic inflammatory skin disease characterized by the presence of activated T cells within the skin.OBJECTIVE: We sought to explore the role of miRNAs in the pathogenesis of atopic dermatitis.METHODS: Global miRNA expression in healthy and lesional skin of patients with atopic dermatitis was compared by using TaqMan MicroRNA Low Density Arrays. miR-155 expression in tissues and cells was quantified by means of quantitative real-time PCR. The cellular localization of miR-155 was analyzed by means of in situ hybridization. The regulation of cytotoxic T lymphocyte-associated antigen (CTLA-4) by miR-155 was investigated by using luciferase reporter assays and flow cytometry. CTLA-4 expression and functional assays were performed on T(H) cells overexpressing miR-155.RESULTS: miR-155 was one of the highest-ranked upregulated miRNAs in patients with atopic dermatitis. In the skin miR-155 was predominantly expressed in infiltrating immune cells. miR-155 was upregulated during T-cell differentiation/activation and was markedly induced by T-cell activators in PBMCs in vitro and by superantigens and allergens in the skin in vivo. CTLA-4, an important negative regulator of T-cell activation, was identified as a direct target of miR-155. Overexpression of miR-155 in T(H) cells resulted in decreased CTLA-4 levels accompanied by an increased proliferative response.CONCLUSION: miR-155 is significantly overexpressed in patients with atopic dermatitis and might contribute to chronic skin inflammation by increasing the proliferative response of T(H) cells through the downregulation of CTLA-4.
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| 2300. |
- Sonkoly, Enikö, et al.
(författare)
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Protein kinase C-dependent upregulation of miR-203 induces the differentiation of human keratinocytes
- 2010
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Ingår i: Journal of Investigative Dermatology. - : Elsevier BV. - 0022-202X .- 1523-1747. ; 130:1, s. 124-134
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Tidskriftsartikel (refereegranskat)abstract
- Terminal differentiation of keratinocytes is a multistep process that requires a coordinated program of gene expression. We aimed to explore the possible involvement of a previously unreported class of non-coding RNA genes, microRNAs (miRNAs) in keratinocyte differentiation by using miRNA expression profiling. Out of 365 miRNAs tested, 7 showed significant change between keratinocytes cultured in low or high calcium concentration. The highest-ranked upregulated gene was miR-203, whose expression was significantly upregulated in response to calcium and other inducers of keratinocyte differentiation such as 12-O-tetradecanoylphorbol-13-acetate (TPA) and vitamin D(3). Differentiation-induced upregulation of miR-203 expression was blocked by treatment with specific inhibitors of protein kinase C (PKC), GF109203X, and Ro31-8220. Moreover, our results showed that the activator protein-1 (AP-1) proteins c-Jun and JunB regulate miR-203 expression in keratinocytes. In contrast to inducers of keratinocyte differentiation, epidermal growth factor and keratinocyte growth factor suppressed miR-203 expression in keratinocytes below the basal level. Overexpression of miR-203 in keratinocytes resulted in enhanced differentiation, whereas inhibition of miR-203 suppressed calcium-induced terminal differentiation as judged by involucrin expression. These results suggest that upregulation of miR-203 in human keratinocytes is required for their differentiation and is dependent on the activation of the PKC/AP-1 pathway.
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