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Pemphigus Vulgaris (PV) is a life-threatening autoimmune disease manifested with blisters in the skin and mucosa and caused by autoantibodies against adhesion protein desmoglein-3 (Dsg3) expressed in epithelial membrane linings of these tissues. Despite many studies, the pathogenesis of PV remains incompletely understood. Recently we have shown Dsg3 plays a role in regulating the yes-associated protein (YAP), a co-transcription factor and mechanical sensor, and constraining reactive oxygen species (ROS). This study investigated the effect of PV sera as well as the anti-Dsg3 antibody AK23 on these molecules. We detected elevated YAP steady-state protein levels in PV cells surrounding blisters and perilesional regions and in keratinocytes treated with PV sera and AK23 with concomitant transient ROS overproduction. Cells treated with hydrogen peroxide also exhibited augmented nuclear YAP accompanied by reduction of Dsg3 and α-catenin, a negative regulator of YAP. As expected, transfection of α-catenin-GFP plasmid rendered YAP export from the nucleus evoked by hydrogen peroxide. In addition, suppression of total YAP was observed in hydrogen peroxide treated cells exposed to antioxidants with enhanced cell-cell adhesion being confirmed by decreased fragmentation in the dispase assay compared to hydrogen peroxide treatment alone. On the other hand, the expression of exogenous YAP disrupted intercellular junction assembly. In contrast, YAP depletion resulted in an inverse effect with augmented expression of junction assembly proteins, including Dsg3 and α-catenin capable of abolishing the effect of AK23 on Dsg3 expression. Finally, inhibition of other kinase pathways, including p38MAPK, also demonstrated suppression of YAP induced by hydrogen peroxide. Furthermore, antioxidant treatment of keratinocytes suppressed PV sera-induced total YAP accumulation. In conclusion, this study suggests that oxidative stress coupled with YAP dysregulation attributes to PV blistering, implying antioxidants may be beneficial in the treatment of PV.

Článek

Hepatocyte and immune cell crosstalk in non-alcoholic fatty liver disease

Expert review of gastroenterology & hepatology. 2021 ; 15 (7) : 783-796. [pub] 20210218

Expert Rev Gastroenterol Hepatol
ISSN 1747-4132
Medvik
Zdroj

Introduction: Nonalcoholic fatty liver disease (NAFLD) is the most widespread chronic liver disease in the world. It can evolve into nonalcoholic steatohepatitis (NASH) where inflammation and hepatocyte ballooning are key participants in the determination of this steatotic state.Areas covered: To provide a systematic overview and current understanding of the role of inflammation in NAFLD and its progression to NASH, the function of the cells involved, and the activation pathways of the innate immunity and cell death; resulting in inflammation and chronic liver disease. A PubMed search was made with relevant articles together with relevant references were included for the writing of this review.Expert opinion: Innate and adaptive immunity are the key players in the NAFLD progression; some of the markers presented during NAFLD are also known to be immunity biomarkers. All cells involved in NAFLD and NASH are known to have immunoregulatory properties and their imbalance will completely change the cytokine profile and form a pro-inflammatory microenvironment. It is necessary to fully answer the question of what initiators and metabolic imbalances are particularly important, considering sterile inflammation as the architect of the disease. Due to the shortage of elucidation of NASH progression, we discuss in this review, how inflammation is a key part of this development and we presume the targets should lead to inflammation and oxidative stress treatment.

MeSH
adaptivní imunita imunologie MeSH
hepatocyty imunologie fyziologie MeSH
interakce mezi receptory a ligandy imunologie fyziologie MeSH
Kupfferovy buňky imunologie MeSH
lidé MeSH
lymfocyty imunologie MeSH
nealkoholová steatóza jater imunologie patofyziologie MeSH
oxidační stres imunologie MeSH
přirozená imunita imunologie MeSH
progrese nemoci MeSH
regulovaná buněčná smrt imunologie fyziologie MeSH
zánět imunologie patofyziologie MeSH
Check Tag
lidé MeSH
Publikační typ
časopisecké články MeSH
přehledy MeSH

Článek

Ambiciózní cíl: vitamínem C pro zdraví - rozhovor

Kotlářová, Lucie, 1974-
Autor Autorita InPharm Clinic, Jesenice u Prahy

Biotherapeutics. 2020 ; 10 (3) : 30-34.

ISSN 1805-1057
Medvik
Zdroj

MeSH
alergologie a imunologie MeSH
kardiovaskulární systém účinky léků MeSH
kyselina askorbová * aplikace a dávkování farmakologie genetika imunologie metabolismus moč MeSH
lidé MeSH
nervový systém - fyziologické jevy MeSH
oxidační stres fyziologie imunologie účinky léků MeSH
psychický stres farmakoterapie patofyziologie MeSH
zdraví MeSH
zdravotnická zařízení MeSH
Check Tag
lidé MeSH
Publikační typ
rozhovory MeSH

Článek

Přínosy askorbátu jako ochrany zdravých buněk v rámci prevence a léčby onkologických onemocnění

Biotherapeutics. 2020 ; 10 (1-2) : 20-28.

ISSN 1805-1057
Medvik
Zdroj

Klíčová slova
P-AscH - vysokodávkový intravenózní vitamin C,
MeSH
antioxidancia terapeutické užití MeSH
antitumorózní látky škodlivé účinky terapeutické užití MeSH
intravenózní podání MeSH
kyselina askorbová aplikace a dávkování farmakokinetika farmakologie MeSH
lidé MeSH
nádory * imunologie patofyziologie MeSH
oxidační stres imunologie účinky léků MeSH
synergismus léků MeSH
vztah mezi dávkou a účinkem léčiva MeSH
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lidé MeSH
Publikační typ
práce podpořená grantem MeSH

Článek

Radiation induces changes in toll-like receptors of the uterine cervix of the rat

PLoS One. 2019 ; 14 (4) : e0215250. [pub] 20190418

ISSN 1932-6203
Medvik
Zdroj

Radiotherapy is an important therapeutic approach against cervical cancer but associated with adverse effects including vaginal fibrosis and dyspareunia. We here assessed the immunological and oxidative responses to cervical irradiation in an animal model for radiation-induced cervicitis. Rats were sedated and either exposed to 20 Gy of ionising radiation given by a linear accelerator or only sedated (controls) and euthanized 1-14 days later. The expressions of toll-like receptors (TLRs) and coupled intracellular pathways in the cervix were assessed with immunohistofluorescence and western blot. Expression of cytokines were analysed with the Bio-Plex Suspension Array System (Bio-Rad). We showed that TLRs 2-9 were expressed in the rat cervix and cervical irradiation induced up-regulation of TLR5, TRIF and NF-κB. In the irradiated cervical epithelium, TLR5 and TRIF were increased in concert with an up-regulation of oxidative stress (8-OHdG) and antioxidant enzymes (SOD-1 and catalase). G-CSF, M-CSF, IL-10, IL- 17A, IL-18 and RANTES expressions in the cervix decreased two weeks after cervical irradiation. In conclusion, the rat uterine cervix expresses the TLRs 2-9. Cervical irradiation induces immunological changes and oxidative stress, which could have importance in the development of adverse effects to radiotherapy.

Článek

The effect of fatty acids in red blood cell membranes on the dynamics of inflammatory markers following the coronary stent implantation

Journal of pharmaceutical and biomedical analysis. 2019 ; 166 (-) : 310-325. [pub] 20190111

J Pharm Biomed Anal
ISSN 1873-264X
Medvik
Zdroj

The effect of 20 fatty acids in erythrocyte cell membranes on the extent of inflammatory response and cell oxidative stress was evaluated using multidimensional statistical data analysis in 54 patients suffering from ischemic heart disease undergoing percutaneous coronary intervention with coronary stent implantation using multidimensional statistical data analysis. A systemic inflammatory response was indicated by an increase of C-reactive protein (CRP), serum amyloid A (SAA) and ceruloplasmin 48 h after stent implantation and by an increase of interleukin-6 (IL-6) 24 h after intervention. The increase of malondialdehyde (MDA) after 48 h was used as a marker of cell damage by oxidative stress. Multiple linear regression revealed statistically significant relationships between concentration of some fatty acids and the magnitude of inflammatory response, or oxidative stress, after stent implantation. The most significant relationship with an increase of plasma CRP was found for myristic acid and, to a lesser extent, for oleic acid. Trans octadecenoic acid, and to a lesser extent palmitooleic and nervonic fatty acids were found in inverse correlation with the CRP increase. The increase of IL-6 showed a statistically significant correlation with myristic acid, to a lesser extent with cis-9-eicosenoic acid and to the least extent with docosahexaenoic acid, inversely with pentadecanoic, γ-linolenic and stearic acids. An increase of oxidative stress (MDA) significantly correlated only with γ-linolenic acid. Other studied markers of inflammatory response to coronary stenting were SAA and ceruloplasmin (Cp). Statistical evaluation revealed that SAA and Cp are not suitable markers for assessment relationships between inflammation and erythrocyte membrane fatty acids.

MeSH
biologické markery krev MeSH
C-reaktivní protein analýza MeSH
erytrocytární membrána imunologie metabolismus MeSH
erytrocyty imunologie metabolismus MeSH
interleukin-6 krev MeSH
koronární angioplastika * MeSH
koronární stenóza krev imunologie terapie MeSH
lidé středního věku MeSH
lidé MeSH
mastné kyseliny metabolismus MeSH
oxidační stres imunologie MeSH
průřezové studie MeSH
sérový amyloid A analýza MeSH
stenty * MeSH
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lidé středního věku MeSH
lidé MeSH
mužské pohlaví MeSH
ženské pohlaví MeSH
Publikační typ
časopisecké články MeSH

Článek

Když lékař najde příčinu, pacienta vyléčí

Biotherapeutics. 2018 ; 8 (4) : 24-28.

ISSN 1805-1057
Medvik
Zdroj

Abstrakt

Příznivé účinky extraktů z červené řepy na hypertenzi, oxidační stres a zánět [Beneficial effects of the red beetroot extrats on hypertension, oxidative stress and inflammation]

Atherosklerosa .... 2017 ; () : 23-27.

ISBN 978-89-905595-4-7
Medvik
Zdroj

Kolekce

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