Effects of (-)-cannabidiol on human sebocytes
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
SUBMITTER: Attila OlM-CM-!h
PROVIDER: E-GEOD-57571 | biostudies-arrayexpress |
REPOSITORIES: biostudies-arrayexpress
Publications
Cannabidiol exerts sebostatic and antiinflammatory effects on human sebocytes.
Oláh Attila A Tóth Balázs I BI Borbíró István I Sugawara Koji K Szöllõsi Attila G AG Czifra Gabriella G Pál Balázs B Ambrus Lídia L Kloepper Jennifer J Camera Emanuela E Ludovici Matteo M Picardo Mauro M Voets Thomas T Zouboulis Christos C CC Paus Ralf R Bíró Tamás T
The Journal of clinical investigation 20140725 9
The endocannabinoid system (ECS) regulates multiple physiological processes, including cutaneous cell growth and differentiation. Here, we explored the effects of the major nonpsychotropic phytocannabinoid of Cannabis sativa, (-)-cannabidiol (CBD), on human sebaceous gland function and determined that CBD behaves as a highly effective sebostatic agent. Administration of CBD to cultured human sebocytes and human skin organ culture inhibited the lipogenic actions of various compounds, including ar ...[more]
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Project description:In the current study, we aimed at exploring the effects of the major non-psychotropic phytocannabinoid of Cannabis sativa, (-)-cannabidiol (CBD), on human sebaceous gland functions. We found that CBD behaved as a highly effective anti-acne agent, targeting all the three key, sebocyte-specific steps of the pathogenesis (i.e. without compromising viability or basal sebaceous lipid production, CBD normalized pro-acne agents-induced excessive lipid synthesis, reduced proliferation and exerted anti-inflammatory actions). The goal of the present microarray analyses was to identify signaling pathways and target genes being involved in mediating the above beneficial effects of CBD.
2014-07-29 | GSE57571 | GEO
Project description:TRPV3 is highly expressed in human skin and is involved in the development of inflammatory dermatoses. However, it remains unclear whether TRPV3 influences inflammation in human sebaceous glands and its role in the pathogenesis of acne. Here, we showed that TRPV3 expression was increased in the sebaceous glands of facial acne lesions and acne-like mice. TRPV3 increased the secretion of pro-inflammatory cytokines and chemokines in human SZ95 sebocytes, as well as the chemotaxis of neutrophils, which were the major immune cells found in acne lesions. We demonstrated that P.acnes promoted TRPV3 expression through regulating lipid profile especially upregulated arachidonic acid levels in human sebocytes. TRPV3 further upregulated TLR2 expression by promoting transcriptional factor p-FOSL1 expression and its binding to the TLR2 promoter, leading to downstream NF-κB signaling activation. Importantly, either genetic silencing or pharmacological inhibition of TRPV3 alleviated acne-like inflammation in mice, showing reduced acne-characteristic cytokines and chemokines production and neutrophil infiltration by inhibiting the TLR2-NF-κB axis. Thus, our study revealed the critical role of TRPV3 in sebocytes inflammation, which was involved in the development of acne, indicating that TRPV3 is a potential therapeutic target for acne and other disorders of the pilosebaceous unit.
2023-10-13 | GSE245001 | GEO
Project description:Background: Possible outcomes of acne lesions are atrophic scars which may cause serious physical and psychological distress. Current treatments of post-acne scarring remain difficult and often require invasive procedures. Pathophysiological studies on acne scaring investigated only the first week of papule life. Objectives: Study the pathophysiology of atrophic acne scar formation to identify molecular and cellular pathways that can lead to new therapies for the prevention of acne scarring. Methods: Large-scale gene expression profiling of uninvolved acne skin and acne papules of 48 hours and 3 weeks of age, respectively, of both, scar-prone (SP) and non-scar-prone (NSP) patients was performed. Immunohistochemistry techniques were applied to confirm transcriptomics results on the protein and cellular level. Results: Gene expression and immunohistochemistry analyses showed a very similar immune response in 48 hours-old papules in SP and NSP populations characterized by elevated numbers of T cells, neutrophils and macrophages. However, only in SP patients the immune response persisted in 3 week-old papules, and was characterized by an important infiltrate of B cells. Transient down-modulation of genes related to lipid metabolism was observed in 48 hours-old papules in NSP patients, followed by normalization of gene expression levels after 3 weeks. In contrast, in SP patients a drastic reduction of lipid metabolizing enzymes was observed in 3 week-old papules, suggesting irreversible modifications. The affected lipid metabolism genes were found preferentially expressed in human sebaceous glands, pointing to a destruction of sebaceous gland structures after 3 weeks of inflammatory remodelling in SP acne patients.
2018-04-30 | GSE108110 | GEO
Project description:Polychlorinated diphenyl ethers are lipophilic, persistent, and bioaccumulable compounds widely used as flame-retardants. These are chemicals of increasing environmental concern due to their lipophilic, persistent, and bioaccumulable characteristics. The objective of this study was to analyze the potential bioavailability and bioaccumulation of BDE-209 as a source of toxicity. Zebrafish embryos were exposed for 8 days to sediments spiked with an environmentally relevant concentration of BDE-209. We analyzed gene expression changes, thyroid function, and several markers for neurotoxicity. Results of this research highlight the need to consider the capability of BDE-209 to be bioavailable and bioaccumulate, indicating the potential hazardous effects. Total RNA was isolated using RNeasy kits (Qiagen, Valencia, CA, USA). The RNA quality was assessed with an Agilent 2100 Bioanalyzer (Agilent, Wilmington, DE, USA) and quantity was determined using a NanodropM-BM-. ND-1000 spectrophotometer. Total RNA was stored at -80oC until analyzed with oligonucleotide microarrays. Zebrafish 44,000 gene arrays (Agilent Single Color 19161, Platform number GPL6457) were purchased from Agilent (Sta. Clara, CA, USA). The Agilent one-color microarray hybridization protocol (One-Color Microarray-Based Gene Expression Analysis, version 5.7, Agilent Technologies, Palo Alto, CA) was used for microarray hybridizations following the manufacturerM-bM-^@M-^Ys protocol and recommendations. Four controls and four treated samples were analyzed, each sample consisting of a pool of embryos. One ug of total RNA was used for all hybridizations. cDNA synthesis, cRNA labeling, amplification and hybridization were performed following the manufacturerM-bM-^@M-^Ys kits and protocols (Quick Amp Labeling kit; Agilent, Palo Alto, CA). An Axon GenePixM-BM-. 4000B Microarray Scanner (Molecular Devices Inc., Sunnyvale, CA) was used to scan microarray images at 5 M-NM-<m resolution. Data were resolved from microarray images using Agilent Feature Extraction software and analyzed using GeneSpring (Agilent Technologies, Palo Alto, CA).
2013-01-01 | E-GEOD-39169 | biostudies-arrayexpress
Project description:The catalytic core of the RNA polymerase of most eubacteria is composed of two M-NM-1 subunits and M-NM-2, M-NM-2M-bM-^@M-^Y and M-OM-^I subunits. In Escherichia coli, the M-OM-^I subunit (encoded by the rpoZ gene) has been suggested to assist M-NM-2M-bM-^@M-^Y during RNA polymerase core assembly. The function of the M-OM-^I subunit is particularly interesting in cyanobacteria because the cyanobacterial M-NM-2M-bM-^@M-^Y is split to N-terminal M-NM-3 and C-terminal M-NM-2M-bM-^@M-^Y subunits. The M-bM-^HM-^FrpoZ strain of the cyanobacterium Synechocystis sp. PCC 6803 grew well in standard conditions although the mutant cells showed low light-saturated photosynthetic activity, low Rubisco content and accumulated high quantities of protective carotenoids and M-NM-1-tocopherol. The M-bM-^HM-^FrpoZ strain contained 15% less of the primary M-OM-^C factor, SigA, than the control strain, and recruitment of SigA to the RNA polymerase core was inefficient in M-bM-^HM-^FrpoZ. Thus, a cyanobacterial RNA polymerase holoenzyme lacking the M-OM-^I subunit contains less frequently the primary M-OM-^C factor. A DNA microarray analysis revealed that this leads to specific down-regulation of highly expressed genes, like genes encoding subunits for Rubisco, ATP synthase, NADH-dehydrogenase and carbon concentrating mechanisms. On the contrary, many genes showing only low or moderate expression in the control strain were up-regulated in M-bM-^HM-^FrpoZ. A conserved -10 region was detected in promoters showing up or down-regulation in M-bM-^HM-^FrpoZ, but -35 regions of down-regulated genes completely differed from -35 regions of up-regulated genes. Cells from cyanobacteria Synechocystis sp. PCC 6803 named as control strain (CS) and RNA polymerase omega subunit inactivation strain, M-NM-^TrpoZ, were harvested (A730=1, 40 mL) directly from standard growth conditions (continuous illumination at the PPFD of 40 M-BM-5mol m-2s-1, 32M-BM-0C, ambient CO2). From three to four independent experiments were performed at each conditions.
2014-01-30 | E-GEOD-51647 | biostudies-arrayexpress
Project description:Adjustment of gene expression during acclimation to stress conditions, such as bright light, in the cyanobacterium Synechocystis sp. PCC 6803 depends on four group 2 M-OM-^C factors (SigB, SigC, SigD, SigE). A M-bM-^HM-^FsigCDE strain containing the stress responsive SigB as an only functional group 2 M-OM-^C factor appears twice as resistant to photoinhibition of photosystem II (PSII) as the control strain. Microarray analyzes of the M-bM-^HM-^FsigCDE strain indicated that 77 genes in standard conditions and 79 genes in high light were differently expressed compared to the control strain. Analysis of possible photoprotective mechanisms revealed that high carotenoid content and up-regulation of the photoprotective flavodiiron operon flv4-sll0218-flv2 protected PSII in M-bM-^HM-^FsigCDE, while up-regulation of pgr5-like, hlipB or isiA genes in the mutant strain did not offer particular protection against photoinhibition. The photoinhibition resistance was lost if M-bM-^HM-^FsigCDE was grown in high CO2 where carotenoid and Flv4-Sll0218-Flv2 contents were low. Additionally, photoinhibition resistance of the M-bM-^HM-^FrpoZ strain (lacking the omega subunit of RNA polymerase) with very high carotenoid but only low Flv4-Sll0218-Flv2 content supported the importance of carotenoids in PSII protection. Carotenoids likely protect mainly via quenching of singlet oxygen but efficient non-photochemical quenching in M-bM-^HM-^FsigCDE might offer some additional protection. Comparison of photoinhibition kinetics in control, M-bM-^HM-^FsigCDE and M-bM-^HM-^FrpoZ strains showed that protection by the flavodiiron operon was most efficient during the first minutes of high-light illumination. Cells from cyanobacteria Synechocystis sp. PCC 6803 named as control strain (CS) and group 2 sigma factor mutant M-NM-^TsigCDE (A730=1, 40 mL) were harvested directly from standard growth conditions (continuous illumination at the PPFD of 40 M-BM-5mol m-2s-1, 32M-BM-0C, ambient CO2) or after 30-min illumination a PPFD 750 M-BM-5mol m-2s-1. From three to four independent experiments were performed at each conditions.
2013-09-20 | E-GEOD-50060 | biostudies-arrayexpress
Project description:Prochloraz is a fungicide known to cause endocrine disruption through effects on the hypothalamic-pituitary-gonadal (HPG) axis. To determine the short-term impacts of prochloraz on gene expression and steroid production, adult female fathead minnows (Pimephales promelas) were exposed to the chemical (0 or 300 M-NM-<g/L) for a time-course of 6, 12 and 24 h. Consistent with inhibition of cytochrome P450 17M-NM-1-hydroxylase/17,20-lyase (CYP17) and aromatase (CYP19), known molecular targets of prochloraz, plasma 17M-NM-2-estradiol (E2) was reduced within 6 hours. Ex vivo E2 production was significantly reduced at all time-points, while ex vivo testosterone (T) production remained unchanged. Consistent with the decrease in E2 levels, plasma concentrations of the estrogen-responsive protein vitellogenin were significantly reduced at 24 h. Genes coding for CYP19, CYP17, and steroidogenic acute regulatory protein were up-regulated in a compensatory manner in ovaries of the prochloraz-treated fish. In addition to targeted quantitative real-time polymerase chain reaction analyses, a 15k feature fathead minnow microarray was used to determine gene expression profiles in ovaries. From time-point to time-point, the microarray results showed a relatively rapid change in the differentially expressed gene (DEG) profiles associated with the chemical exposure. Functional analysis of the DEGs indicated changes in expression of genes associated with cofactor and coenzyme binding (GO: 0048037 and 0050662), fatty acid binding (GO:0005504) and organelle organization and biogenesis (GO: 0006996). Overall, the results from this study are consistent with compensation of the fish HPG axis to inhibition of steroidogenesis by prochloraz, and provide further insights into relatively rapid, system-wide, effects of a model chemical stressor on fish. RNA samples for each treatment/time point combination were used for microarray analysis (total of 23 arrays). For the microarray work, total RNA was isolated from ovary samples using RNeasy kits (Qiagen, Valencia, CA, USA). The RNA quality was assessed with an Agilent 2100 Bioanalyzer (Agilent, Wilmington, DE, USA) and quantity was determined using a NanodropM-BM-. ND-1000 spectrophotometer. Total RNA was stored at -80oC until analyzed with oligonucleotide microarrays. Microarray analysis was conducted at the US Army Engineer Research and Development Center (Vicksburg, MS, USA) using a 15k feature fathead minnow microarray (GEO: http://www.ncbi.nlm.nih.gov/geo/; Accession platform number GPL9248) designed by Dr. Nancy Denslow (University of Florida, Gainesville, FL, USA) and manufactured by Agilent Technologies (Palo Alto, CA, USA). The Agilent one-color microarray hybridization protocol (One-Color Microarray-Based Gene Expression Analysis, version 5.7, Agilent Technologies) was used for microarray hybridizations. One M-BM-5g of total RNA was used for all hybridizations. The cDNA synthesis, cRNA labeling, amplification and hybridization were performed following the manufacturerM-bM-^@M-^Ys kits and protocols (Quick Amp Labeling kit; Agilent Technologies). An Axon GenePixM-BM-. 4000B Microarray Scanner (Molecular Devices Inc., Sunnyvale, CA, USA) was used to scan microarray images at 5 M-NM-<m resolution. Data were resolved from microarray images using Agilent Feature Extraction software (Agilent Technologies). Statistical analyses were conducted using Statistica 8 (StatSoft Inc., Tulsa, OK, USA) and GraphPad Instat v. 3.01 (GraphPad Software, San Diego, CA, USA). Data were tested for normality and homogeneity of variance. When data conformed to parametric assumptions, data were analyzed using a parametric one-way ANOVA with chemical treatment as the independent variable. When data did not conform to parametric assumptions, they were either transformed (log 10) or analyzed using a non-parametric KruskallM-bM-^@M-^SWallis test (pM-bM-^IM-$ 0.05). The data are presented as means with standard errors of the mean. Differences were considered significant at p M-bM-^IM-$ 0.05. Microarray data were imported into the Rosetta Resolver 7.2 system for gene expression analysis (Rosetta Biosoftware, Kirkland, WA, USA). Data were normalized using the default, text loader, intensity profile builder settings in the Rosetta Resolver system. Significantly DEGs were identified using one-way ANOVA (p < 0.01) with no multiple testing correction
2011-02-03 | E-GEOD-26958 | biostudies-arrayexpress
Project description:Diethylstilbestrol (DES) is a synthetic estrogen that has been banned for use in humans, but still is employed in livestock and aquaculture operations in some parts of the world. Detectable concentrations of DES in effluent and surface waters have been reported to range from slightly below 1 to greater than 10 ng/L. Little is known, however, concerning the toxicological potency of DES in fish. In this study, sexually-mature fathead minnows (Pimephales promelas) of both sexes were exposed to 1, 10 or 100 ng DES/L water in a flow-through system. Tissue concentrations of DES and changes in a number of estrogen-responsive endpoints, including alterations to the hepatic transcriptome in females, were measured in the fish at the end of a 4-d exposure, and after a 4-d depuration/recovery period in clean water. The objectives of the study were to measure accumulation of DES in fish tissues, characterize effects of the chemical on physiological endpoints related to reproductive performance, and to evaluate DES's potency relative to concentrations reported in aquatic environments. The current series includes n=12 microarrays associated with exposure-phase samples (collected from fish exposed continuously for 4 d). Fish were exposed to 0, 1, 10, or 100 ng DES/L delivered in a continuous flow (45 ml/min) of sand filtered, UV treated, Lake Superior Water, without the use of carrier solvents. Flow of DES into the test system was initiated without fish present and continued for 1 d. Exposures then were started by placing three male and three female sexually-mature fathead minnows into each tank. There were eight replicate tanks for the control and 100 ng/L treatments, and six replicate tanks for the 1 and 10 ng/L groups. The fish were held at 25+1M-BM-:C under a 16:8 L:D photoperiod and were fed frozen adult brine shrimp twice daily (San Francisco Bay Brand, Newark, CA, USA). Fish used for the experiment were from an on-site culture, and all procedures involving animals conformed to guidelines approved by the local Animal Care and Use Committee. After the 4-d exposure, fish from three tanks from each treatment (n=9 per sex) were sampled for determination of various biological endpoints. At this time fish from two additional tanks from the control and 100 ng/L treatments also were sampled for determination of DES tissue residues (n=6 per sex). Delivery of DES to the test system was subsequently stopped, and fish from the remaining three tanks per treatment group were sampled 4 d later (n= 9 per sex). The fathead minnows were euthanized with buffered MS-222 (Argent, Redmond, VA, USA) and weighed. Fish were scored for occurrence and relative expression of nuptial tubercles, which in males can be reduced by ER agonists. Blood was collected from the caudal vein/artery with a microhematocrit tube, and plasma was separated by centrifugation and stored at -80M-BM-:C. Gonads were removed from males and a subsample (8.5M-BM-13.0 mg; meanM-BM-1SD) was immediately immersed in tissue culture media for determination of ex vivo steroid production. Livers were removed from both sexes and flash-frozen for gene expression analyses using microarray (females) or real-time QPCR (males). Hepatic transcripts from three females per treatment group, in each phase of the experiment (except n=2 from recovery phase 10 ng/L) were analyzed using a custom 15,000 feature microarray (GEO Platform Accession GPL9248). Data sets for the exposure phase (n=12 microarrays) and recovery phase (n=11) were normalized independently using Fastlo (Ballman et al., 2004) implemented in R (http://www.r-project.org/), but analyzed using parallel approaches.
2012-09-20 | E-GEOD-36465 | biostudies-arrayexpress
Project description:Interpretation of toxicogenomic experiments conducted with ovary tissue from asynchronous-spawning small fish species are complicated by background variation in the relative abundance and proportion of follicles at different stages within the ovary tissue sample. This study employed both real-time quantitative PCR and a 15,000 gene oligonucleotide microarray to examine variation in the fathead minnow (Pimephales promelas) ovarian transcriptional profile as a function of quantitative and qualitative differences in ovarian histology. Multiple lines of evidence supported the conclusion that variation in the transcriptional profile was primarily dependent on the relative abundance of previtellogenic versus vitellogenic follicles in the ovary tissue. Due to the relatively small proportions of mature ovulated follicles or atretic follicles in the overall follicle population, few putative molecular markers of maturation, ovulation, or atresia could be identified. However, among the 460 differentially expressed genes identified in the study, targets including HtrA serine peptidase 3 (htra3), tissue inhibitor of metalloproteinase 3 (timp3), aquaporin 8 (aqp8), transgelin 2 like (tagln2), Nedd4 family interacting protein 2 (ndfip2), chemokine ligand 12a (cxcl12a), midkine related growth factor (mdka), and jagged 1b (jag 1b) exhibited responses and functional properties that support them as candidate molecular markers of significant shift in gross ovarian stage. Overall, results of this study provide insights into background variation in ovary transcript profiles that should aid and enhance the interpretation of toxicogenomic data generated in experiments conducted with small, asynchronous spawning fish species. Relative abundance of approximately 15,000 RNA transcripts in 26 ovary samples and 4 expelled oocyte (egg) samples, representing the five different histoclasses defined for the present study, was evaluated using fathead minnow oligonucleotide microarrays. Fathead minnow 15,000 gene arrays were purchased from Agilent (Palo Alto, CA, USA). The Agilent one-color microarray hybridization protocol (One-Color Microarray-Based Gene Expression Analysis, version 5.7, Agilent Technologies, Palo Alto, CA) was used for microarray hybridizations following the manufacturerM-bM-^@M-^Ys protocol and recommendations. One ug of total RNA was used for all hybridizations. cDNA synthesis, cRNA labeling, amplification and hybridization were performed following the manufacturerM-bM-^@M-^Ys kits and protocols (Quick Amp Labeling kit; Agilent, Palo Alto, CA). An Axon GenePixM-BM-. 4000B Microarray Scanner (Molecular Devices Inc., city, state) was used to scan microarray images at 5 M-NM-<m resolution.
2010-04-30 | E-GEOD-18254 | biostudies-arrayexpress
Project description:Diethylstilbestrol (DES) is a synthetic estrogen that has been banned for use in humans, but still is employed in livestock and aquaculture operations in some parts of the world. Detectable concentrations of DES in effluent and surface waters have been reported to range from slightly below 1 to greater than 10 ng/L. Little is known, however, concerning the toxicological potency of DES in fish. In this study, sexually-mature fathead minnows (Pimephales promelas) of both sexes were exposed to 1, 10 or 100 ng DES/L water in a flow-through system. Tissue concentrations of DES and changes in a number of estrogen-responsive endpoints, including alterations to the hepatic transcriptome in females, were measured in the fish at the end of a 4-d exposure, and after a 4-d depuration/recovery period in clean water. The objectives of the study were to measure accumulation of DES in fish tissues, characterize effects of the chemical on physiological endpoints related to reproductive performance, and to evaluate DES's potency relative to concentrations reported in aquatic environments. The current series includes n=11 microarrays associated with recovery-phase samples (collected from fish exposed continuously for 4 d, and then held in control water for an additional 4 days before tissues were collected). Fish were exposed to 0, 1, 10, or 100 ng DES/L delivered in a continuous flow (45 ml/min) of sand filtered, UV treated, Lake Superior Water, without the use of carrier solvents. Flow of DES into the test system was initiated without fish present and continued for 1 d. Exposures then were started by placing three male and three female sexually-mature fathead minnows into each tank. There were eight replicate tanks for the control and 100 ng/L treatments, and six replicate tanks for the 1 and 10 ng/L groups. The fish were held at 25+1M-BM-:C under a 16:8 L:D photoperiod and were fed frozen adult brine shrimp twice daily (San Francisco Bay Brand, Newark, CA, USA). Fish used for the experiment were from an on-site culture, and all procedures involving animals conformed to guidelines approved by the local Animal Care and Use Committee. After the 4-d exposure, fish from three tanks from each treatment (n=9 per sex) were sampled for determination of various biological endpoints. At this time fish from two additional tanks from the control and 100 ng/L treatments also were sampled for determination of DES tissue residues (n=6 per sex). Delivery of DES to the test system was subsequently stopped, and fish from the remaining three tanks per treatment group were sampled 4 d later (n= 9 per sex). The fathead minnows were euthanized with buffered MS-222 (Argent, Redmond, VA, USA) and weighed. Fish were scored for occurrence and relative expression of nuptial tubercles, which in males can be reduced by ER agonists. Blood was collected from the caudal vein/artery with a microhematocrit tube, and plasma was separated by centrifugation and stored at -80M-BM-:C. Gonads were removed from males and a subsample (8.5M-BM-13.0 mg; meanM-BM-1SD) was immediately immersed in tissue culture media for determination of ex vivo steroid production. Livers were removed from both sexes and flash-frozen for gene expression analyses using microarray (females) or real-time QPCR (males). Hepatic transcripts from three females per treatment group, in each phase of the experiment (except n=2 from recovery phase 10 ng/L) were analyzed using a custom 15,000 feature microarray (GEO Platform Accession GPL9248). Data sets for the exposure phase (n=12 microarrays) and recovery phase (n=11) were normalized independently using Fastlo (Ballman et al., 2004) implemented in R (http://www.r-project.org/), but analyzed using parallel approaches.
2012-09-20 | E-GEOD-36466 | biostudies-arrayexpress