• MeSH
• buněčná imunita MeSH
• imunologické testy MeSH
• lidé MeSH
• lymfocyty MeSH
• melanom MeSH
• nemoci uvey MeSH
• techniky in vitro MeSH
• Check Tag
• lidé MeSH

• MeSH
• imunoglobuliny MeSH
• Orthomyxoviridae imunologie   MeSH
• techniky tkáňových kultur využití   MeSH
• vakcíny proti chřipce aplikace a dávkování   MeSH

• MeSH
• aktivní imunita MeSH
• dialýza ledvin metody   MeSH
• imunosupresiva terapeutické užití   MeSH
• myozitida diagnóza   terapie   MeSH
• Publikační typ
• kazuistiky MeSH

Anaplasma phagocytophilum is an emerging pathogen that causes human granulocytic anaplasmosis. Infection with this zoonotic pathogen affects cell function in both vertebrate host and the tick vector, Ixodes scapularis. Global tissue-specific response and apoptosis signaling pathways were characterized in I. scapularis nymphs and adult female midguts and salivary glands infected with A. phagocytophilum using a systems biology approach combining transcriptomics and proteomics. Apoptosis was selected for pathway-focused analysis due to its role in bacterial infection of tick cells. The results showed tissue-specific differences in tick response to infection and revealed differentiated regulation of apoptosis pathways. The impact of bacterial infection was more pronounced in tick nymphs and midguts than in salivary glands, probably reflecting bacterial developmental cycle. All apoptosis pathways described in other organisms were identified in I. scapularis, except for the absence of the Perforin ortholog. Functional characterization using RNA interference showed that Porin knockdown significantly increases tick colonization by A. phagocytophilum. Infection with A. phagocytophilum produced complex tissue-specific alterations in transcript and protein levels. In tick nymphs, the results suggested a possible effect of bacterial infection on the inhibition of tick immune response. In tick midguts, the results suggested that A. phagocytophilum infection inhibited cell apoptosis to facilitate and establish infection through up-regulation of the JAK/STAT pathway. Bacterial infection inhibited the intrinsic apoptosis pathway in tick salivary glands by down-regulating Porin expression that resulted in the inhibition of Cytochrome c release as the anti-apoptotic mechanism to facilitate bacterial infection. However, tick salivary glands may promote apoptosis to limit bacterial infection through induction of the extrinsic apoptosis pathway. These dynamic changes in response to A. phagocytophilum in I. scapularis tissue-specific transcriptome and proteome demonstrated the complexity of the tick response to infection and will contribute to characterize gene regulation in ticks.

• MeSH
• Anaplasma phagocytophilum genetika   patogenita   MeSH
• anaplasmóza genetika   mikrobiologie   přenos   MeSH
• apoptóza genetika   MeSH
• buněčná diferenciace genetika   MeSH
• hmyz - vektory genetika   mikrobiologie   MeSH
• klíště mikrobiologie   MeSH
• lidé MeSH
• orgánová specificita MeSH
• regulace genové exprese MeSH
• RNA interference MeSH
• signální transdukce genetika   MeSH
• slinné žlázy metabolismus   mikrobiologie   MeSH
• systémová biologie * MeSH
• transkriptom genetika   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

Glucocorticoids influence the function of numerous tissues. Although there are a very large number of studies that have investigated the local metabolism of glucocorticoids in mammals, the knowledge of this metabolism in birds is limited. The local concentration of corticosterone is critical for both glucocorticoid- and mineralocorticoid-dependent activity, and we have therefore carried out studies of corticosterone metabolism in various chicken organs. It was found that corticosterone was metabolized to 20-dihydrocorticosterone, and in some tissues also to 11-dehydrocorticosterone and 11-dehydro-20-dihydrocorticosterone. The activity of 20-hydroxysteroid dehydrogenase (20HSD), responsible for the transformation of corticosterone to 20-hydroxy derivatives, was abundant in the kidney and intestine, with lower levels in the liver and testis. Low levels of 20HSD were detected in the brain and ovaries. In contrast, 11-hydroxysteroid dehydrogenase (11HSD) activity was only found in the kidney and intestine. No activity was observed in the brain, testis, or ovaries. The treatment of chickens with estrogens stimulated 20HSD activity in the kidney, intestine, and oviduct and 11HSD activity in the liver and oviduct. Kinetic studies for corticosterone yielded an apparent Km for 11HSD in the nanomolar (Km = 21 +/- 5 nmol.l(-1)) and for 20HSD in the micromolar range (Km = 3.7 +/- 0.3 micromol.l(-1)). When progesterone or 5alpha-dihydrotestosterone were used instead of corticosterone, the tissues reduced the former to 20beta-dihydroprogesterone and the latter to both 5alpha,3alpha- and 5alpha,3beta-dihydrotestosterone. The data presents the first evidence for corticosterone metabolism via 11beta-, 3alpha/3beta-, and 20beta-hydroxysteroid dehydrogenases in various chicken organs and provide support for the theory of prereceptor modulation of glucocorticoid signals in avian tissues.

• MeSH
• 11-beta-hydroxysteroiddehydrogenasy metabolismus   MeSH
• 20-hydroxysteroid dehydrogenasy metabolismus   MeSH
• financování organizované MeSH
• kortikosteron metabolismus   MeSH
• kur domácí fyziologie   MeSH
• orgánová specificita MeSH
• tkáňová distribuce MeSH
• zvířata MeSH
• Check Tag
• zvířata MeSH
• Publikační typ
• srovnávací studie MeSH

Mutual interactions between adipocytes and immune cells in white adipose tissue (WAT) are involved in modulation of lipid metabolism in the tissue and also in response to omega-3 polyunsaturated fatty acids (PUFA), which counteract adverse effects of obesity. This complex interplay depends in part on in situ formed anti- as well as pro-inflammatory lipid mediators, but cell types engaged in the synthesis of the specific mediators need to be better characterized. We used tissue fractionation and metabolipidomic analysis to identify cells producing lipid mediators in epididymal WAT of mice fed for 5 weeks obesogenic high-fat diet (lipid content 35% wt/wt), which was supplemented or not by omega-3 PUFA (4.3 mg eicosapentaenoic acid and 14.7 mg docosahexaenoic acid per g of diet). Our results demonstrate selective increase in levels of anti-inflammatory lipid mediators in WAT in response to omega-3, reflecting either their association with adipocytes (endocannabinoid-related N-docosahexaenoylethanolamine) or with stromal vascular cells (pro-resolving lipid mediator protectin D1). In parallel, tissue levels of obesity-associated pro-inflammatory endocannabinoids were suppressed. Moreover, we show that adipose tissue macrophages (ATMs), which could be isolated using magnetic force from the stromal vascular fraction, are not the major producers of protectin D1 and that omega-3 PUFA lowered lipid load in ATMs while promoting their less-inflammatory phenotype. Taken together, these results further document specific roles of various cell types in WAT in control of WAT inflammation and metabolism and they suggest that also other cells but ATMs are engaged in production of pro-resolving lipid mediators in response to omega-3 PUFA.

• MeSH
• antiflogistika aplikace a dávkování   MeSH
• aplikace orální MeSH
• bílá tuková tkáň cytologie   účinky léků   imunologie   MeSH
• buňky stromatu účinky léků   imunologie   MeSH
• imunologické faktory imunologie   MeSH
• kultivované buňky MeSH
• makrofágy cytologie   účinky léků   imunologie   MeSH
• metabolismus lipidů účinky léků   imunologie   MeSH
• myši inbrední C57BL MeSH
• myši MeSH
• omega-3 mastné kyseliny aplikace a dávkování   MeSH
• potravní doplňky MeSH
• tukové buňky účinky léků   enzymologie   imunologie   MeSH
• zvířata MeSH
• Check Tag
• mužské pohlaví MeSH
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

Disruption of cell division cycle associated 7 (CDCA7) has been linked to aberrant DNA hypomethylation, but the impact of DNA methylation loss on transcription has not been investigated. Here, we show that CDCA7 is critical for maintaining global DNA methylation levels across multiple tissues in vivo. A pathogenic Cdca7 missense variant leads to the formation of large, aberrantly hypomethylated domains overlapping with the B genomic compartment but without affecting the deposition of H3K9 trimethylation (H3K9me3). CDCA7-associated aberrant DNA hypomethylation translated to localized, tissue-specific transcriptional dysregulation that affected large gene clusters. In the brain, we identify CDCA7 as a transcriptional repressor and epigenetic regulator of clustered protocadherin isoform choice. Increased protocadherin isoform expression frequency is accompanied by DNA methylation loss, gain of H3K4 trimethylation (H3K4me3), and increased binding of the transcriptional regulator CCCTC-binding factor (CTCF). Overall, our in vivo work identifies a key role for CDCA7 in safeguarding tissue-specific expression of gene clusters via the DNA methylation pathway.

• MeSH
• DNA MeSH
• jaderné proteiny * metabolismus   MeSH
• metylace DNA MeSH
• myši MeSH
• protein - isoformy genetika   MeSH
• proteiny buněčného cyklu * metabolismus   MeSH
• represorové proteiny genetika   MeSH
• transkripční faktory genetika   MeSH
• zvířata MeSH
• Check Tag
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

Sepsis is a life threatening condition that arises when the body's response to an infection injures its own tissues and organs. Sepsis can lead to shock, multiple organ failure and death especially if not recognized early and treated promptly. Molecular mechanisms underlying the systemic inflammatory response syndrome associated with sepsis are still not completely defined and most therapies developed to target the acute inflammatory component of the disease are insufficient. In this study we investigated a possibility of combating sepsis in a mouse model by intravenous treatment with recombinant human tissue non-specific alkaline phosphatase (rhTNAP) derived from transgenic rabbit milk. We induced sepsis in mice by intraperitoneal injection of LPS and three hours later treated experimental group of mice by intravenous injection with rhTNAP derived from transgenic rabbits. Such treatment was proved to be physiologically effective in this model, as administration of recombinant rhTNAP successfully combated the decrease in body temperature and resulted in increased survival of mice (80 % vs. 30 % in a control group). In a control experiment, also the administration of bovine intestinal alkaline phosphatase by intravenous injection proved to be effective in increasing survival of mice treated with LPS. Altogether, present work demonstrates the redeeming effect of the recombinant tissue non-specific AP derived from milk of genetically modified rabbits in combating sepsis induced by LPS.

• MeSH
• alkalická fosfatasa terapeutické užití   MeSH
• geneticky modifikovaná zvířata MeSH
• králíci MeSH
• lidé MeSH
• lipopolysacharidy toxicita   MeSH
• míra přežití trendy   MeSH
• myši inbrední BALB C MeSH
• myši MeSH
• pilotní projekty MeSH
• rekombinantní proteiny terapeutické užití   MeSH
• sepse chemicky indukované   farmakoterapie   mortalita   MeSH
• skot MeSH
• zvířata MeSH
• Check Tag
• králíci MeSH
• lidé MeSH
• mužské pohlaví MeSH
• myši MeSH
• skot MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

The C-547 is the most effective muscle and tissue-specific anticholinesterase among alkylammonium derivatives of 6-methyluracil (ADEMS) acting in nanomolar concentrations on locomotor muscles but not on respiratory muscles, smooth muscles and heart and brain acetylcholine esterases (AChE). When applied systematically it could influence peripheral acetylcholine receptors. The aim of the present study was to investigate the effect of C-547 on rat α3β4 (ganglionic type) and αβεδ (muscle type) nicotinic receptors expressed in COS cells. Currents evoked by rapid application of acetylcholine or nicotine were recorded in whole-cell mode by electrophysiological patch-clamp technique 2-4 days after cell transfection by plasmids coding the α3β4 or αβεδ combination of receptor subunits. In cells sensitive to acetylcholine, the application of C-547 evoked no responses. When acetylcholine was applied during an already running application of C-547, acetylcholine responses were only inhibited at concentrations higher than 10(-7)M. This inhibition is not voltage-dependent, but is accompanied by an increased rate of desensitization. Thus in both types of receptors, effective doses are approximately 100 times higher than those inhibiting AChE in leg muscles and similar to those inhibiting respiratory diaphragm muscles and external intercostal muscles. These observations show that C-547 can be considered for symptomatic treatment of myasthenia gravis and other congenital myasthenic syndromes as an inhibitor of AChE in leg muscles at concentrations much lower than those inhibiting muscle and ganglion types of acetylcholine receptors.

• MeSH
• acetylcholin farmakologie   MeSH
• acetylcholinesterasa metabolismus   MeSH
• Cercopithecus aethiops MeSH
• cholinesterasové inhibitory farmakologie   MeSH
• COS buňky MeSH
• ganglia účinky léků   metabolismus   MeSH
• krysa rodu rattus MeSH
• kvartérní amoniové sloučeniny farmakologie   MeSH
• nikotinové receptory metabolismus   MeSH
• orgánová specificita MeSH
• podjednotky proteinů metabolismus   MeSH
• svaly účinky léků   metabolismus   MeSH
• uracil analogy a deriváty   farmakologie   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu rattus MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

• MeSH
• buněčná imunita MeSH
• imunologické techniky MeSH
• melanom imunologie   MeSH
• nemoci uvey imunologie   MeSH