Staphylococcus Aureus and Streptococcus Pyogenes Induce Psoriasis-Related Transcriptomes in Human Keratinocytes Augmented by IL-17A and TNF-α
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PROVIDER: PRJNA854972 | ENA |
REPOSITORIES: ENA
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Project description:This study aims to define the interactions that SA or SP may have with IL-17A and TNF-α in human keratinocytes, as well as the similarity to psoriasis vulgaris
2023-03-24 | GSE207390 | GEO
Project description:In psoriasis lesions, a diverse mixture of cytokines is upregulated which influence each other generating a complex inflammatory situation. Although this is the case, the inhibition of Interleukin-17A (IL-17A) alone showed unprecedented clinical results in patients, indicating that IL-17A is a critical inducer of psoriasis pathogenesis. To elucidate IL-17A-driven keratinocyte-intrinsic signaling pathways, we treated monolayers of normal human epidermal keratinocytes in vitro with a mixture of 6 cytokines (IL-17A, TNF-a, IL-17C, IL-22, IL-36g and IFN-g) involved in psoriasis, to mimic the inflammatory milieu in psoriasis lesions. Microarray and gene set enrichment analysis revealed that this cytokine mixture induced similar gene expression changes with the previous transcriptome studies using psoriasis lesions. Importantly, we identified a set of IL-17A-regulated genes in keratinocytes, which recapitulate typical psoriasis genes exemplified by DEFB4A, S100A7, IL19 and CSF3, based on differences in the expression profiles of cells stimulated with 6 cytokines versus cells stimulated with only 5 cytokines lacking IL-17A. Furthermore a specific IL-17A-induced gene, NFKBIZ, which encodes IkappaB-zeta, a transcriptional regulator for NF-kappaB, was demonstrated to have a significant role for IL-17A-induced gene expression. Thus, we present novel in vitro data from normal human keratinocytes that would help elucidating the IL-17A-driven keratinocyte activation in psoriasis. Cytokine mixture-induced gene expression in primary normal human epidermal keratinocytes (NHEKs) was measured at 24 hours after exposure. NHEKs were exposed to the combination of selected six cytokines (IL-17A: 100 ng/ml, TNF-a: 10 ng/ml, IFN-g: 10 ng/ml, IL-17C: 100 ng/ml, IL-22: 100 ng/ml, IL-36g: 500 ng/ml) , or to the different combinations of five of the six cytokines (in total, 7 different treatments and one untreated control). No replicate experiments were conducted.
2016-03-08 | E-GEOD-77719 | biostudies-arrayexpress
Project description:In psoriasis lesions, a diverse mixture of cytokines is upregulated which influence each other generating a complex inflammatory situation. Although this is the case, the inhibition of Interleukin-17A (IL-17A) alone showed unprecedented clinical results in patients, indicating that IL-17A is a critical inducer of psoriasis pathogenesis. To elucidate IL-17A-driven keratinocyte-intrinsic signaling pathways, we treated monolayers of normal human epidermal keratinocytes in vitro with a mixture of 6 cytokines (IL-17A, TNF-a, IL-17C, IL-22, IL-36g and IFN-g) involved in psoriasis, to mimic the inflammatory milieu in psoriasis lesions. Microarray and gene set enrichment analysis revealed that this cytokine mixture induced similar gene expression changes with the previous transcriptome studies using psoriasis lesions. Importantly, we identified a set of IL-17A-regulated genes in keratinocytes, which recapitulate typical psoriasis genes exemplified by DEFB4A, S100A7, IL19 and CSF3, based on differences in the expression profiles of cells stimulated with 6 cytokines versus cells stimulated with only 5 cytokines lacking IL-17A. Furthermore a specific IL-17A-induced gene, NFKBIZ, which encodes IkappaB-zeta, a transcriptional regulator for NF-kappaB, was demonstrated to have a significant role for IL-17A-induced gene expression. Thus, we present novel in vitro data from normal human keratinocytes that would help elucidating the IL-17A-driven keratinocyte activation in psoriasis.
2016-03-08 | GSE77719 | GEO
Project description:Here, we identified psoriasis-associated genes upregulated by TWEAK stimulation, alone or in combination with either TNF or IL-17, in human keratinocytes.
2021-11-19 | GSE171170 | GEO
Project description:In this study we tested interactions between IL-36 and IL-17A in human keratinocytes. 24 hours of IL-36 stimulation in keratinocytes promoted IL-36, IL-17C, and characteristic psoriasis-related molecule expressions in normal human epidermal keratinocytes in dose-dependent manners as measured by mRNA and protein quantification.
2021-12-31 | GSE160904 | GEO
Project description:We sought to provide a comprehensive evaluation of the effects of TNF-α and IL-17 on the keratinocyte gene profile in order to identify genes that might be co-regulated by these cytokines. We then sought to determine how genes that were synergistically activated by both cytokines relate to the psoriasis transcriptome. Here, we identified 160 unique genes that were synergistically up-regulated by IL-17 and TNF-α and 188 unique genes where the two cytokines had at least an additive effect. Among highly up-regulated genes were those involved in neutrophil and lymphocyte chemotaxis, inflammation, and epidermal differentiation. Synergistically up-regulated genes included some of the highest expressed genes in lesional psoriatic skin with an impressive correlation between IL-17/TNF-α induced genes and the psoriasis gene signature. In conclusion, keratinocytes may be key drivers of pathogenetic inflammatory circuits in psoriasis through integrating responses to TNF-α and IL-17. This may explain high efficacy of targeting psoriasis with either anti-TNF-α or agents that block Th17 T-cells/IL-17 and has important implications for the development of new therapeutic agents. Comparison of keratinocyte responses to IL-17, TNF-α (1 ng mL-1 and 10 ng mL-1), and the combination of both cytokines in psoriasis.
2010-11-24 | E-GEOD-24767 | biostudies-arrayexpress
Project description:Adalimumab and secukinumab are commonly used for moderate-severe psoriasis vulgaris (PV), but distinct individual response and impaired effectiveness happen occasionally. Little is known about it. Here, we report a proteomic analysis of psoriatic lesions from patients treated with these drugs using Data Independent Acquisition Mass Spectrometry (DIA-MS). Thousands of differentially expressed proteins (DEPs) changed over 12 weeks of treatment. Network analysis showed DEPs could interact and induce transformation in matrix components, metabolic regulation, and immune response. PRM analysis suggested S100s, STAT1, KRT2, TYMP, SOD2, HSP90AB1, TFRC, and COL5A1 were the most significantly changed proteins in both groups. There is a positively association between the psoriasis area and severity index (PASI) score and three proteins (TFRC, IMPDH2, KRT2). Our study suggests that inhibition of IL-17A and TNF-α can induce multiple molecules change in psoriatic lesions and overlapping effect on immune response and proces
2022-10-20 | PXD037579 |
Project description:Psoriasis is a chronic immune-mediated skin condition influenced by genetics and environmental factors. γδ T cells, as the main sources of IL-17A, play pivotal roles in the inflammatory processes of psoriasis. During psoriasis pathogenesis, inhibiting the secretion of IL-17A has emerged as a novel therapeutic approach for treating psoriasis. Double-negative T (DNT) cells is a novel type of immunosuppressive cells. Our preliminary research has unveiled that DNT cells play a significant immunoregulatory role in autoimmune and allergic diseases. In this study, we aimed to evaluate the protection of DNT cells and explore its underlying mechanism.
2024-04-10 | GSE248626 | GEO
Project description:The clinical features of psoriasis, characterized by sharply demarcated scaly erythematous plaques, are typically so distinctive that a diagnosis can easily be made on these grounds alone. However, there is great variability in treatment response between individual patients, and this may reflect heterogeneity of inflammatory networks driving the disease. In this study, whole-genome transcriptional profiling was used to characterize inflammatory and cytokine networks in 62 lesional skin samples obtained from patients with stable chronic plaque psoriasis. We were able to stratify lesions according to their inflammatory gene expression signatures, identifying those associated with strong (37% of patients), moderate (39%) and weak inflammatory infiltrates (24%). Additionally, we identified differences in cytokine signatures with heightened cytokine-response patterns in one sub-group of lesions (IL-13-strong; 50%) and attenuation of these patterns in a second sub-group (IL-13-weak; 50%). These sub-groups correlated with the composition of the inflammatory infiltrate, but were only weakly associated with increased risk allele frequency at some psoriasis susceptibility loci (e.g., REL, TRAF3IP2 and NOS2). Our findings highlight variable points in the inflammatory and cytokine networks known to drive chronic plaque psoriasis. Such heterogeneous aspects may shape clinical course and treatment responses, and can provide avenues for development of personalized treatments. We used Affymetrix microarrays to evaluate genome-wide expression in primary human keratinocytes exposed to cytokines. Cytokine activity signatures were used to interpret the shifts in gene expression that occur in psoriasis plaques relative to normal uninvolved skin. Primary keratinocytes from three donors (subjects 1, 2, and 3) were obtained and were either untreated (control) or exposed to cytokines (IL-4, IL-13, IFN-alpha, IFN-gamma and TNF). For the IL17A samples, primary keratinocytes were obtained from six donors, with cells derived from three donors treated with IL-17A and cells derived from the other three donors left untreated (i.e., unpaired control samples).
2012-03-07 | E-GEOD-36287 | biostudies-arrayexpress
Project description:We sought to provide a comprehensive evaluation of the effects of TNF-α and IL-17 on the keratinocyte gene profile in order to identify genes that might be co-regulated by these cytokines. We then sought to determine how genes that were synergistically activated by both cytokines relate to the psoriasis transcriptome. Here, we identified 160 unique genes that were synergistically up-regulated by IL-17 and TNF-α and 188 unique genes where the two cytokines had at least an additive effect. Among highly up-regulated genes were those involved in neutrophil and lymphocyte chemotaxis, inflammation, and epidermal differentiation. Synergistically up-regulated genes included some of the highest expressed genes in lesional psoriatic skin with an impressive correlation between IL-17/TNF-α induced genes and the psoriasis gene signature. In conclusion, keratinocytes may be key drivers of pathogenetic inflammatory circuits in psoriasis through integrating responses to TNF-α and IL-17. This may explain high efficacy of targeting psoriasis with either anti-TNF-α or agents that block Th17 T-cells/IL-17 and has important implications for the development of new therapeutic agents.
2010-11-24 | GSE24767 | GEO