High-Throughput RNA Sequencing Reveals the Effect of NB- UVB Phototherapy on Major Inflammatory Molecules of Lesional Psoriasis
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE179632 | GEO | 2023/03/22
REPOSITORIES: GEO
Similar Datasets
Project description:Psoriasis is a common chronic inflammatory and hyperproliferative immune-mediated skin disorder. Narrow-band UVB (NB-UVB) phototherapy is a convenient first-line treatment of psoriasis, though the mechanisms underlying its efficacy have not been completely elucidated. In order to improve our understanding of NB-UVB phototherapy, gene expression profiling was used to characterize gene expression in lesional epidermis from psoriasis patients undergoing NB-UVB phototherapy. Increased expression of melanogenesis pathway genes was observed to be the earliest response. At the end of treatment, genes involved in diverse biological processes were affected, such as pigmentation, cell adhesion, ectodermal development and metabolism. The relationship between gene expression and treatment outcome was further studied using Partial Least Squares Discriminant Analysis (PLS-DA). Gene ontology analysis showed that genes responding to phototherapy and highly correlated to treatment outcome were involved in oxidation reduction, growth and mitochondria organization. In particular SPATA18, a key regulator of mitochondria quality, was found to be significantly downregulated in psoriasis, and its upregulation following phototherapy was required for optimal clinical improvement. Our data suggest that oxidation reduction is a critical event for the resolution of psoriatic plaques. Twelve patients diagnosed with plaque type psoriasis were recruited to the study. NB-UVB irradiation was administered to the whole body two to three times a week. Treatment comprising approximately 24 sessions was given during two to three months. A total of six 4 mm diameter punch biopsies were taken from lesions on each psoriasis patient: two prior to UV treatment (pre-UV), two at the middle stage of UV treatment (after about one month of treatment, mid-UV) and two before the last treatment session (post-UV). Twelve healthy age-, sex- and skin type-matched volunteers were also recruited and two punch biopsies were taken from the buttocks. RNA was extracted from Laser capture microdissected epidermis.
2013-12-23 | E-GEOD-53431 | biostudies-arrayexpress
Project description:Psoriasis is a common chronic inflammatory and hyperproliferative immune-mediated skin disorder. Narrow-band UVB (NB-UVB) phototherapy is a convenient first-line treatment of psoriasis, though the mechanisms underlying its efficacy have not been completely elucidated. In order to improve our understanding of NB-UVB phototherapy, gene expression profiling was used to characterize gene expression in lesional epidermis from psoriasis patients undergoing NB-UVB phototherapy. Increased expression of melanogenesis pathway genes was observed to be the earliest response. At the end of treatment, genes involved in diverse biological processes were affected, such as pigmentation, cell adhesion, ectodermal development and metabolism. The relationship between gene expression and treatment outcome was further studied using Partial Least Squares Discriminant Analysis (PLS-DA). Gene ontology analysis showed that genes responding to phototherapy and highly correlated to treatment outcome were involved in oxidation reduction, growth and mitochondria organization. In particular SPATA18, a key regulator of mitochondria quality, was found to be significantly downregulated in psoriasis, and its upregulation following phototherapy was required for optimal clinical improvement. Our data suggest that oxidation reduction is a critical event for the resolution of psoriatic plaques.
2013-12-23 | GSE53431 | GEO
Project description:Background: Atopic dermatitis (AD) is a common inflammatory skin disease with broad impact on quality of life and on the health care system. The pathophysiology is not fully understood, but it is likely multifactorial involving immune dysfunction, altered skin barrier and environmental factors. Narrow band ultraviolet B (nb-UVB) treatment leads to normalization of the tissue and clinical improvement. However, knowledge of early changes in AD skin in response to nb-UVB is lacking and could provide important clues to decipher the disease mechanisms and potential new treatment targets. Objective: To map the early transcriptional changes in the skin in response to nb-UVB treatment. Results: When examining the early response after only three local UVB-treatments, gene expression analysis revealed 30 down- and 47 up-regulated transcripts. Among these only a small proportion were related to the inflammatory response. Interestingly, two cytokines of the interleukin (IL)-1 family were differentially expressed: the proinflammatory cytokine IL-36γ was reduced after treatment, while the anti-inflammatory cytokine IL-37 increased in skin after treatment with nb-UVB. Conclusion: Local nb-UVB induced an early decrease of the pro-inflammatory cytokine IL-36γ and an increase of the anti-inflammatory IL-37. This likely represents one of the first changes in inflammatory signaling induced by nb-UVB in atopic eczema.
2020-10-27 | GSE150797 | GEO
Project description:Background: Atopic dermatitis (AD) is a common inflammatory skin disease exhibiting a predominantly Th2/“T22” immune activation and a defective epidermal barrier. Narrow-band UVB (NB-UVB) is considered an efficient treatment for moderate to severe AD. In psoriasis, NB-UVB has been found to suppress the Th1/Th17 immune polarization with subsequent reversal of epidermal hyperplasia. The immunomodulatory effects of this treatment are largely unknown in AD. Our study evaluates the effects of NB-UVB on immune and barrier abnormalities in AD, aiming to establish reversibility of disease and biomarkers of therapeutic response. Methods: 12 moderate-to-severe chronic AD patients received NB-UVB phototherapy 3 times weekly for up to 12 weeks. Lesional and non-lesional skin biopsies were obtained before and after treatment and evaluated by gene-expression and immunohistochemistry studies. Results: All patients had at least a 50% reduction in SCORing of AD (SCORAD) index with NB-UVB phototherapy. The Th2, T22, and Th1 immune pathways were suppressed and measures of epidermal hyperplasia and differentiation also normalized after phototherapy. The reversal of disease activity was associated with elimination of inflammatory leukocytes, Th2/“T22”-associated cytokines and chemokines, and normalized expression of barrier proteins. Conclusions: Our study shows reversal of both the epidermal defects and underlying immune activation in AD. By determining the correlation of variables with therapeutic response, we have defined a set of biomarkers of disease response that associate resolved Th2 and T22 inflammation with reversal of barrier pathology. This data supports the “inside-out” hypothesis of AD, suggesting that it is a disease primarily driven by an immune stimulus.
2011-07-01 | GSE27887 | GEO
Project description:Background: Atopic dermatitis (AD) is a common inflammatory skin disease exhibiting a predominantly Th2/"T22" immune activation and a defective epidermal barrier. Narrow-band UVB (NB-UVB) is considered an efficient treatment for moderate to severe AD. In psoriasis, NB-UVB has been found to suppress the Th1/Th17 immune polarization with subsequent reversal of epidermal hyperplasia. The immunomodulatory effects of this treatment are largely unknown in AD. Our study evaluates the effects of NB-UVB on immune and barrier abnormalities in AD, aiming to establish reversibility of disease and biomarkers of therapeutic response. Methods: 12 moderate-to-severe chronic AD patients received NB-UVB phototherapy 3 times weekly for up to 12 weeks. Lesional and non-lesional skin biopsies were obtained before and after treatment and evaluated by gene-expression and immunohistochemistry studies. Results: All patients had at least a 50% reduction in SCORing of AD (SCORAD) index with NB-UVB phototherapy. The Th2, T22, and Th1 immune pathways were suppressed and measures of epidermal hyperplasia and differentiation also normalized after phototherapy. The reversal of disease activity was associated with elimination of inflammatory leukocytes, Th2/"T22"-associated cytokines and chemokines, and normalized expression of barrier proteins. Conclusions: Our study shows reversal of both the epidermal defects and underlying immune activation in AD. By determining the correlation of variables with therapeutic response, we have defined a set of biomarkers of disease response that associate resolved Th2 and T22 inflammation with reversal of barrier pathology. This data supports the "inside-out" hypothesis of AD, suggesting that it is a disease primarily driven by an immune stimulus. genomic profiling of treatment effect of NB-UVB in AD in both lesional and non-lesional AD skin from 10 patients. Treatment effect, disease state analysis
2011-07-01 | E-GEOD-27887 | biostudies-arrayexpress
Project description:We sought to define the cutaneous response at 24 hours following erythemogenic doses of narrow-band UVB (NB-UVB, 312 nm peak) exposure and determine the differences between irradiated and non-irradiated skin. Comparison of Transcriptome between NB-UVB irradiated (2MED) and non-irradiated skin (NON IRRAD).
2012-10-30 | E-GEOD-41078 | biostudies-arrayexpress
Project description:We report the high-throughput profiling of tissue biopsy in peri- lesion from psoriasis skin before the start of NB-UVB therapy and after treatment.RNA sequencing (RNA-Seq) was conducted to assay the transcriptomes and identify differentially expressed transcripts enriched in major pathway analysis.
2023-03-22 | GSE179731 | GEO
Project description:We sought to define the cutaneous response at 24 hours following erythemogenic doses of narrow-band UVB (NB-UVB, 312 nm peak) exposure and determine the differences between irradiated and non-irradiated skin.
2012-10-30 | GSE41078 | GEO
Project description:To obtain a comprehensive DNA methylation signature specific for the epidermal component of psoriasis and to analyze methylation changes during therapy, we performed genome-wide DNA methylation profiling of epidermal cells from 12 patients undergoing narrow-band UVB phototherapy and 12 corresponding healthy controls. A distinct DNA methylation pattern was seen in psoriasis compared to controls. An overall hypomethylation was found in psoriasis and 3665 methylation variable positions were identified. The DNA methylation pattern was reversed at the end of phototherapy in patients with clinical response. Bisulphite converted DNA from the 47 samples were hybridised to the Illumina Infinium 450k Human Methylation Beadchip.
2015-04-02 | E-GEOD-63315 | biostudies-arrayexpress
Project description:Considering that human skin cancer is predominantly attributed to UV radiation from sunlight, additional investigations are needed to elucidate the role of P2RY6 in UVB-induced skin carcinogenesis. Surprisingly, we find that P2ry6 deletion exhibits marked promotion to UVB-induced skin papilloma formation compared with wild-type mice, suggesting its tumor-suppressive role in UVB-induced skin cancer. Additionally, P2ry6 knockout promotes mouse skin hyperplasia induced by short-term UVB irradiation, while UDP, the ligand of P2RY6, can inhibit UVB-induced skin damage. Furthermore, UVB irradiation can significantly upregulate P2RY6 expression in mouse and human skin cells. These results indicate that P2RY6 plays a crucial protective role in resisting UVB-induced skin damage and carcinogenesis. At the molecular level, P2RY6 deletion inhibits ubiquitination and expression of XPC after UVB irradiation in keratinocytes, resulting in the accumulation of CPDs (cyclobutane pyrimidine dimers). P2RY6 deletion also activates PI3K/AKT signaling pathway in vitro and in vivo. The CPD accumulation and inflammatory responses enhanced by P2RY6 deletion are reversed by an AKT inhibitor. These findings suggest that P2RY6 acts as a tumor suppressor in UVB-induced skin cancer by regulating PI3K/AKT signaling pathway.
2024-01-16 | GSE251675 | GEO