Psoriasis is a chronic non-contagious autoimmune disease. Gallic acid is a natural compound with potential health benefits, including antioxidant, anticancer, antiviral and antibacterial properties. Nevertheless, the influence of gallic acid on psoriasis has not been fully determined. This investigation aimed to discover the effect of gallic acid on psoriasis. Thirty-one pairs of psoriatic skin tissues and healthy adult human skin tissues were collected. Human keratinocytes (HaCaT cells) were transfected with interleukin 17A (IL-17A) to create the psoriatic keratinocyte model. The content of bromodomain-containing protein 4 (BRD4) microRNA was assessed using qRT-PCR testing. The content of BRD4 was detected by Western blotting. Cell migration was evaluated by conducting a wound healing assay. Cell proliferation was determined using an EdU assay. Apoptosis was detected by the TUNEL assay. The contents of interferon gamma (IFN-γ), IL-6, IL-8 and IL-17 were detected by ELISA. BRD4 was up-regulated in psoriatic skin tissues and in the IL-17A group compared to the healthy adult human skin tissues and the control group. Silencing BRD4 inhibited cell migration, proliferation and inflammatory response but induced apoptosis in IL-17A-treated HaCaT cells. Conversely, BRD4 over-expression promoted cell migration, proliferation and inflammatory response but suppressed apoptosis in IL-17A-treated HaCaT cells. Gallic acid repressed cell migration, proliferation and inflammatory response but indu-ced apoptosis in HaCaT cells transfected with IL-17A by down-regulating BRD4. Gallic acid represses cell migration, proliferation and inflammatory response but induces apoptosis in IL-17A-transfected HaCaT cells by down-regulating BRD4.
- MeSH
- apoptóza * účinky léků MeSH
- buněčné linie keratinocytů HaCaT MeSH
- buněčné linie MeSH
- dospělí MeSH
- interleukin-17 metabolismus MeSH
- jaderné proteiny metabolismus genetika MeSH
- keratinocyty * účinky léků metabolismus MeSH
- kyselina gallová * farmakologie MeSH
- lidé MeSH
- mikro RNA genetika metabolismus MeSH
- pohyb buněk * účinky léků MeSH
- proliferace buněk * účinky léků MeSH
- proteiny buněčného cyklu * metabolismus genetika MeSH
- proteiny obsahující bromodoménu MeSH
- psoriáza * metabolismus patologie farmakoterapie MeSH
- regulace genové exprese účinky léků MeSH
- transkripční faktory * metabolismus MeSH
- zánět * patologie MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
BACKGROUND: Psoriasis is a pathological condition characterized by immune system dysfunction and inflammation. Patients with psoriasis are more likely to develop a wide range of disorders associated with inflammation. Serum levels of various substances and their combinations have been associated with the presence of the disease (psoriasis) and have shown the potential to reflect its activity. The aim of the present study is to contribute to the elucidation of pathophysiological links between psoriasis, its pro-inflammatory comorbidity metabolic syndrome (MetS), and the expression of clusterin and elafin, which are reflected in the pathophysiological "portfolio" of both diseases. MATERIAL AND METHODS: Clinical examinations (PASI score), ELISA (clusterin, elafin), and biochemical analyses (parameters of MetS) were performed. RESULTS: We found that patients with psoriasis were more often afflicted by MetS, compared to the healthy controls. Clusterin and elafin levels were higher in the patients than in the controls but did not correlate to the severity of psoriasis. CONCLUSION: Our data suggest that patients with psoriasis are more susceptible to developing other systemic inflammatory diseases, such as MetS. The levels of clusterin and elafin, which are tightly linked to inflammation, were significantly increased in the patients, compared to the controls, but the presence of MetS in patients did not further increase these levels.
- MeSH
- dospělí MeSH
- elafin genetika MeSH
- index tělesné hmotnosti MeSH
- klusterin genetika MeSH
- komorbidita MeSH
- lidé středního věku MeSH
- lidé MeSH
- metabolický syndrom komplikace genetika metabolismus patologie MeSH
- psoriáza komplikace genetika metabolismus patologie MeSH
- regulace genové exprese genetika MeSH
- studie případů a kontrol MeSH
- stupeň závažnosti nemoci MeSH
- zánět genetika metabolismus patologie MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
Gentiana lutea is a bitter herb that is traditionally used to improve gastric disorders. Recently, we have shown that Gentiana lutea extract (GE) also modulates the lipid metabolism of human keratinocytes in vitro and in vivo. In the present study, we investigated the role of GE on ceramide synthesis in human primary keratinocytes (HPKs) and psoriasis-like keratinocytes. We could demonstrate that GE increased the concentrations of glucosylceramides and the ceramide AS/AdS subclass without affecting the overall ceramide content in HPKs. The expression of ceramide synthase 3 (CERS3) and elongases (ELOVL1 and 4) was reduced in psoriasis lesions compared to healthy skin. Psoriasis-like HPKs, generated by stimulating HPKs with cytokines that are involved in the pathogenesis of psoriasis (IL-17, TNF-α, IL-22 and IFN-γ) showed increased levels of IL-6, IL-8 and increased expression of DEFB4A, as well as decreased expression of ELOVL4. The treatment with GE partly rescued the reduced expression of ELOVL4 in psoriasis-like HPKs and augmented CERS3 expression. This study has shown that GE modulates ceramide synthesis in keratinocytes. Therefore, GE might be a novel topical treatment for skin diseases with an altered lipid composition such as psoriasis.
- MeSH
- ceramidy metabolismus MeSH
- elongasy mastných kyselin genetika metabolismus MeSH
- Gentiana chemie MeSH
- keratinocyty cytologie účinky léků metabolismus MeSH
- kultivované buňky MeSH
- lidé MeSH
- membránové proteiny genetika metabolismus MeSH
- metabolismus lipidů účinky léků MeSH
- oční proteiny genetika metabolismus MeSH
- primární buněčná kultura MeSH
- psoriáza genetika metabolismus MeSH
- regulace genové exprese účinky léků MeSH
- rostlinné extrakty chemie farmakologie MeSH
- sfingosin-N-acyltransferasa genetika metabolismus MeSH
- studie případů a kontrol MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
In the pathogenesis of psoriasis, systemic inflammation and oxidative stress play mutual roles interrelated with metabolic syndrome (MetS). This study aims to map the selected markers of inflammation (C-reactive protein (CRP)), oxidative damage to nucleic acids (DNA/RNA damage; 8-hydroxy-2'-deoxyguanosine, 8-hydroxyguanosine, and 8-hydroxyguanine), and the parameters of MetS (waist circumference, fasting glucose, triglycerides, high-density lipoprotein (HDL) cholesterol, diastolic and systolic blood pressure) in a group of 37 patients with psoriasis (62% of MetS) and in 43 healthy controls (42% of MetS). Levels of CRP, DNA/RNA damage, fasting glucose, and triglycerides were significantly elevated in patients. MetS in conjunction with psoriasis was associated with high levels of CRP, significantly higher than in control subjects without MetS. Patients with MetS exhibited further DNA/RNA damage, which was significantly higher in comparison with the control group. Our study supports the independent role of psoriasis and MetS in the increase of CRP and DNA/RNA damage. The psoriasis contributes to an increase in the levels of both effects more significantly than MetS. The psoriasis also diminished the relationship between CRP and oxidative damage to nucleic acids existent in controls.
- MeSH
- lidé středního věku MeSH
- lidé MeSH
- metabolický syndrom komplikace MeSH
- oxidační stres * MeSH
- poškození DNA * MeSH
- psoriáza etiologie metabolismus patofyziologie MeSH
- zánět komplikace MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
BACKGROUND: Ultraviolet radiation (UVR) and crude coal tar (CCT) containing PAHs can accelerate the skin-aging process (SAP). However, UVR induces the formation of an important protective factor in SAP (vitamin D). OBJECTIVE: To determine the relation of SAP to selected risks and benefits of combined dermal exposure to UVR and coal tar (PAHs). METHODS: The study group consisted of patients with chronic stable plaque psoriasis and treated by Goeckerman therapy (GT; daily dermal application of UVR and 5% CCT ointment). The levels of urinary 1-hydroxypyrene (1-OHP), oxidative stress (DNA and RNA damage), genotoxic damage (chromosomal aberration in peripheral lymphocytes; ABC), 25-hydroxy-vitamin D [25(OH)D] and the PASI score were evaluated before and after GT. RESULTS: Intensive dermal absorption of PAHs was confirmed by increased levels of 1-OHP (p<0.01). After the therapy, we found an increased level of oxidative stress (p<0.05), an increased level of genotoxic damage (ABC; p<0.001), a high efficiency of the treatment (p<0.001) and an elevated production of 25(OH)D (p<0.01). We also found a relationship between the duration of UVR and the genotoxic damage (p<0.01), vitD (p<0.05) and the PASI score (p<0.05). Furthermore, we found a relationship between oxidative stress and 25(OH)D (p<0.05) and between genotoxic damage and the PASI score (p<0.05). CONCLUSION: Dermal exposure to UVR and coal tar (PAHs) enhances the level of oxidative stress and genotoxic damage and thus contributes to SAP. However, the exposure is very effective as a treatment and elevates the production of 25(OH)D, the protective factor in SAP. According to our results, UVR is probably a more hazardous factor in SAP.
- MeSH
- aplikace kožní MeSH
- biologické markery krev moč MeSH
- časové faktory MeSH
- celotělové ozáření MeSH
- chronická nemoc MeSH
- dehet uhelný aplikace a dávkování škodlivé účinky MeSH
- dospělí MeSH
- keratolytika aplikace a dávkování škodlivé účinky MeSH
- kombinovaná terapie MeSH
- kouření škodlivé účinky MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladý dospělý MeSH
- oxidační stres účinky léků účinky záření MeSH
- polycyklické aromatické uhlovodíky aplikace a dávkování škodlivé účinky MeSH
- poškození DNA MeSH
- psoriáza diagnóza metabolismus terapie MeSH
- pyreny moč MeSH
- senioři MeSH
- stabilita RNA účinky léků účinky záření MeSH
- stárnutí kůže účinky léků účinky záření MeSH
- terapie ultrafialovými paprsky škodlivé účinky metody MeSH
- vitamin D analogy a deriváty krev MeSH
- výsledek terapie MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladý dospělý MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Epigenetic modifications are essential regulators of biological processes. Decreased DNA methylation of OAS2 (2'-5'-Oligoadenylate Synthetase 2), encoding an antiviral protein, has been seen in psoriasis. To provide further insight into the epigenetic regulation of OAS2, we performed pyrosequencing to detect OAS2 DNA methylation status at 11 promoter and first exon located CpG sites in psoriasis (n = 12) and two common subtypes of squamous cell carcinoma (SCC) of the head and neck: tongue (n = 12) and tonsillar (n = 11). Compared to corresponding controls, a general hypomethylation was seen in psoriasis. In tongue and tonsillar SCC, hypomethylation was found at only two CpG sites, the same two sites that were least demethylated in psoriasis. Despite differences in the specific residues targeted for methylation/demethylation, OAS2 expression was upregulated in all conditions and correlations between methylation and expression were seen in psoriasis and tongue SCC. Distinctive methylation status at four successively located CpG sites within a genomic area of 63 bp reveals a delicately integrated epigenetic program and indicates that detailed analysis of individual CpGs provides additional information into the mechanisms of epigenetic regulation in specific disease states. Methylation analyses as clinical biomarkers need to be tailored according to disease-specific sites.
- MeSH
- 2',5'-oligoadenylátsynthetasa genetika metabolismus MeSH
- CpG ostrůvky * MeSH
- epigeneze genetická * MeSH
- lidé MeSH
- metylace DNA MeSH
- nádory hlavy a krku genetika metabolismus patologie MeSH
- nádory jazyka genetika metabolismus patologie MeSH
- promotorové oblasti (genetika) MeSH
- psoriáza genetika metabolismus patologie MeSH
- retrospektivní studie MeSH
- spinocelulární karcinom genetika metabolismus patologie MeSH
- studie případů a kontrol MeSH
- tonzilární nádory genetika metabolismus patologie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Chronická ložisková psoriáza je chronické erytématoskvamózne ochorenie, ktoré postihuje 2–3 % populácie. V etiopatogenéze stredne ťažkej až ťažkej formy psoriázy dochádza ku vzniku veľkého množstva prozápalových cytokínov (TNFα, IL6, IL17, IL20, IL23), ktoré následne ovplyvňujú ostatné orgány a vedú k chronickému systémovému zápalu. Stredne ťažká až ťažká psoriáza je asociovaná s tzv. kardiometabolickými komorbiditami, z ktorých najvýznamnejší je metabolický syndróm. Etiopatogenéza psoriázy je prepojená s patogenézou metabolického syndrómu. Ochorenia majú spoločný genetický základ a produkujú navzájom stimulujúce cytokíny. Celý kolobeh prozápalových cytokínov má vplyv na zvýšenie kardiovaskulárneho rizika a to najmä u mladých pacientov so závažnými formami ochorenia. Skoré zahájenie systémovej a biologickej liečby psoriázy, edukácia a prísne sledovanie komorbidít pacienta môžu zabrániť v rozvoji metabolického syndrómu a zvýšeného kardiovaskulárneho rizika.
x
Psoriasis is an inflammatory skin disease that affects 2-5% of the worldwide population. It is a chronic immune-mediated hyperproliferative inflammatory skin disease of unknown etiology, characterized by the appearance of sore patches of thick, red skin with silvery scales.
- MeSH
- fibroblasty účinky léků metabolismus MeSH
- kůže cytologie patologie MeSH
- lidé MeSH
- oleje rostlin chemie farmakologie MeSH
- oxidace-redukce účinky léků MeSH
- psoriáza metabolismus patologie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
The paper presents a prospective cohort study. Observed group was formed of children with plaque psoriasis (n=19) treated by Goeckerman therapy (GT). The study describes adverse (side) effects associated with application of GT (combined exposure of 3% crude coal tar ointment and UV radiation). After GT we found significantly increased markers of oxidative stress (8-hydroxy-2'-deoxyguanosine, 8-hydroxyguanosine, and 8-hydroxyguanine), significantly increased levels of benzo[a]pyrene-7,8-diol-9,10-epoxide (BPDE) DNA adducts (BPDE-DNA), and significantly increased levels of total number of chromosomal aberrations in peripheral lymphocytes. We found significant relationship between (1) time of UV exposure and total number of aberrated cells and (2) daily topical application of 3% crude coal tar ointment (% of body surface) and level of BPDE-DNA adducts. The findings indicated increased hazard of oxidative stress and genotoxic effects related to the treatment. However, it must be noted that the oxidized guanine species and BPDE-DNA adducts also reflect individual variations in metabolic enzyme activity (different extent of bioactivation of benzo[a]pyrene to BPDE) and overall efficiency of DNA/RNA repair system. The study confirmed good effectiveness of the GT (significantly decreased PASI score).
- MeSH
- 7,8-dihydro-7,8-dihydroxybenzo(a)pyren 9,10-oxid analýza chemie MeSH
- adukty DNA analýza chemie MeSH
- benzopyren chemie toxicita MeSH
- chromozomální aberace * MeSH
- dehet uhelný farmakologie terapeutické užití MeSH
- dítě MeSH
- DNA chemie MeSH
- keratolytika farmakologie terapeutické užití MeSH
- kohortové studie MeSH
- lidé MeSH
- lymfocyty cytologie metabolismus MeSH
- masti farmakologie terapeutické užití MeSH
- mladiství MeSH
- oxidační stres účinky léků MeSH
- poškození DNA účinky léků MeSH
- předškolní dítě MeSH
- prospektivní studie MeSH
- psoriáza farmakoterapie metabolismus patologie MeSH
- ultrafialové záření * MeSH
- Check Tag
- dítě MeSH
- lidé MeSH
- mladiství MeSH
- mužské pohlaví MeSH
- předškolní dítě MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- MeSH
- diabetes mellitus 2. typu diagnóza prevence a kontrola MeSH
- hodnocení rizik MeSH
- hypertenze diagnóza farmakoterapie prevence a kontrola MeSH
- ischemická choroba srdeční diagnóza farmakoterapie prevence a kontrola MeSH
- lidé MeSH
- metabolický syndrom diagnóza etiologie terapie MeSH
- obezita diagnóza prevence a kontrola MeSH
- prediabetes diagnóza metabolismus MeSH
- psoriáza komplikace metabolismus MeSH
- Check Tag
- lidé MeSH