p38 mitogen-activated protein kinase (MAPK) is an important protein which plays a key role in regulating the innate immunity, so exploring its molecular characterization is helpful in understanding the resistance against microbial infections in cultured fish. Here, a full-length cDNA of p38 MAPK was cloned from liver of blunt snout bream (Megalobrama amblycephala) which covered 2419 bp with an open reading frame of 1086 bp encoding 361 amino acids. p38 MAPK contained the characteristic structures of Thr-Gly-Tyr (TGY) motif and substrate binding site Ala-Thr-Arg-Trp (ATRW), which are conserved in MAPK family. To investigate p38 MAPK functions, two in vivo experiments were carried out to examine its expression following ammonia exposure and bacterial challenge. Also, an in vitro experiment was conducted to assess the role of p38 MAPK in inflammation of primary hepatocytes induced by lipopolysaccharide (LPS). The results showed the ubiquitous expression of p38 MAPK in all the tested tissues with varying levels. p38 MAPK mRNA expression was significantly up-regulated by ammonia stress and Aeromonas hydrophila challenge, and altered in a time-dependent manner. Moreover, the results indicated that the inflammatory response induced by LPS in hepatocytes is p38 MAPK dependent as knockdown of p38 MAPK using siRNA technology depressed the expression of IL-1β and IL-6. The findings in this study showed that p38 MAPK has anti-stress property, and plays key role in protection against bacterial infection and inflammation in blunt snout bream.

• MeSH
• Aeromonas hydrophila fyziologie   MeSH
• amoniak škodlivé účinky   MeSH
• buněčná imunita genetika   MeSH
• Cyprinidae genetika   imunologie   MeSH
• fylogeneze MeSH
• gramnegativní bakteriální infekce imunologie   MeSH
• lipopolysacharidy farmakologie   MeSH
• mitogenem aktivované proteinkinasy p38 chemie   genetika   imunologie   MeSH
• náhodné rozdělení MeSH
• nemoci ryb imunologie   MeSH
• přirozená imunita genetika   MeSH
• regulace genové exprese imunologie   MeSH
• rybí proteiny chemie   genetika   imunologie   MeSH
• sekvence aminokyselin MeSH
• sekvence nukleotidů MeSH
• sekvenční seřazení veterinární   MeSH
• stanovení celkové genové exprese veterinární   MeSH
• zvířata MeSH
• Check Tag
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

The elevated plasma cell-free DNA (cfDNA) concentrations were repeatedly reported in association with the process of inflammation. The qualitative and quantitative characteristics of plasma cfDNA in active (newly diagnosed) celiac disease patients (CD) have not yet been studied despite the fact that cfDNA of healthy individuals is able to regulate immune response. We determined the total cfDNA concentration and relative content of telomeric sequences in plasma cfDNA in CD (n = 10) and healthy age- and sex-matched controls (HC, n = 10) by quantitative PCR. To obtain the evidence that the observed biological effects are caused solely by cfDNA molecules, we applied the treatment of paired plasma samples with DNase. Using paired samples of plasma (non-treated/native and treated by DNase), we analyzed the contribution of cfDNA to the activation of TLR9 and TNF-α mRNA expression in THP1 monocytic cell line. There were no significant differences in the quantities of plasma cfDNA and relative contents of telomeric sequences in their pools. When we compared the levels of TNF-α mRNA expression in THP1 cells achieved after stimulation with native CD and HC plasma samples, we found significantly (p = .031) higher expression after stimulation with CD samples. We documented also the ability of cfDNA contained in CD plasma samples to stimulate the production of TLR9 mRNA. The TLR9 mRNA expression levels were significantly (p = .014) lowered after cfDNA removal from CD plasma samples. The design of our experiments allowed us to study the effects of cfDNA without its isolation from plasma. cfDNA contained in CD plasma samples differs significantly in its immunoregulatory capacity from cfDNA in HC plasma. The differences are caused neither by different concentrations of cfDNA in plasma samples nor by different relative abundance of telomeric sequences. Further studies are needed to elucidate the role of plasma cfDNA in celiac disease pathogenesis.

• MeSH
• celiakie krev   MeSH
• dospělí MeSH
• imunologické faktory * krev   imunologie   farmakologie   MeSH
• kvantitativní polymerázová řetězová reakce MeSH
• lidé MeSH
• pilotní projekty MeSH
• regulace genové exprese * účinky léků   imunologie   MeSH
• THP-1 buňky MeSH
• TNF-alfa * biosyntéza   imunologie   MeSH
• toll-like receptor 9 * biosyntéza   imunologie   MeSH
• volné cirkulující nukleové kyseliny * krev   imunologie   farmakologie   MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

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.

• MeSH
• adaptorové proteiny vezikulární transportní imunologie   MeSH
• cervix uteri imunologie   patologie   MeSH
• cytokiny imunologie   MeSH
• experimentální radiační poranění imunologie   patologie   MeSH
• krysa rodu rattus MeSH
• NF-kappa B imunologie   MeSH
• oxidační stres imunologie   účinky záření   MeSH
• potkani Sprague-Dawley MeSH
• regulace genové exprese imunologie   účinky záření   MeSH
• toll-like receptory imunologie   MeSH
• zánět děložního hrdla imunologie   patologie   MeSH
• záření gama škodlivé účinky   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu rattus MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

Helminths and bacteria are major players in the mammalian gut ecosystem and each influences the host immune system and health. Declines in helminth prevalence and bacterial diversity appear to play a role in the dramatic rise of immune mediated inflammatory diseases (IMIDs) in western populations. Helminths are potent modulators of immune system and their reintroduction is a promising therapeutic avenue for IMIDs. However, the introduction of helminths represents a disturbance for the host and it is important to understand the impact of helminth reintroduction on the host, including the immune system and gut microbiome. We tested the impact of a benign tapeworm, Hymenolepis diminuta, in a rat model system. We find that H. diminuta infection results in increased interleukin 10 gene expression in the beginning of the prepatent period, consistent with induction of a type 2 immune response. We also find induction of humoral immunity during the patent period, shown here by increased IgA in feces. Further, we see an immuno-modulatory effect in the small intestine and spleen in patent period, as measured by reductions in tissue immune cells. We observed shifts in microbiota community composition during the patent period (beta-diversity) in response to H. diminuta infection. However, these compositional changes appear to be minor; they occur within families and genera common to both treatment groups. There was no change in alpha diversity. Hymenolepis diminuta is a promising model for helminth therapy because it establishes long-term, stable colonization in rats and modulates the immune system without causing bacterial dysbiosis. These results suggest that the goal of engineering a therapeutic helminth that can safely manipulate the mammalian immune system without disrupting the rest of the gut ecosystem is in reach.

• MeSH
• Bacteria klasifikace   izolace a purifikace   MeSH
• biodiverzita MeSH
• biologické modely * MeSH
• feces chemie   MeSH
• fylogeneze MeSH
• Hymenolepis diminuta imunologie   MeSH
• imunitní systém * MeSH
• imunoglobulin A analýza   imunologie   MeSH
• interakce hostitele a parazita imunologie   MeSH
• interleukin-10 genetika   metabolismus   MeSH
• krysa rodu rattus MeSH
• potkani Wistar MeSH
• regulace genové exprese imunologie   MeSH
• slezina imunologie   MeSH
• střeva mikrobiologie   parazitologie   MeSH
• střevní mikroflóra * MeSH
• zvířata MeSH
• Check Tag
• krysa rodu rattus MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

This study tested the hypothesis that neuropeptide Y (NPY) and NPY receptors 1 (Y1) and 2 (Y2) participate in lung allograft rejection. Inflammation in grafts may include interaction between blood leukocytes and graft endothelial cells and marked accumulation of intravascular blood leukocytes. Fewer leukocytes accumulate in lung than in kidney allografts. Lung transplantion was performed in the Dark Agouti to Lewis rat strain combination. Intravascular and intraalveolar leukocytes were isolated from the grafts, and we evaluated the mRNA expression of NPY, Y1, and Y2 by real-time RT-PCR as well as the peptide expression of NPY by radioimmunoassay and immunohistochemistry. NPY and Y1 were expressed by pulmonary intravascular and intraalveolar leukocytes. Y1 was up-regulated by pulmonary intravascular and intraalveolar leukocytes during allograft rejection while Y2 could not be detected. Higher NPY expression levels in intravascular leukocytes were observed in lung compared to kidney allografts, which were investigated previously. Our findings suggest that an increased leukocytic expression of NPY in lung compared to kidney allografts results in a reduced accumulation of leukocytes in allograft vessels.

• MeSH
• akutní nemoc MeSH
• alografty MeSH
• krysa rodu rattus MeSH
• leukocyty imunologie   patologie   MeSH
• neuropeptid Y imunologie   MeSH
• plíce imunologie   patologie   MeSH
• potkani inbrední LEW MeSH
• receptory neuropeptidu Y imunologie   MeSH
• receptory neuropeptidů imunologie   MeSH
• receptory spřažené s G-proteiny imunologie   MeSH
• regulace genové exprese imunologie   MeSH
• rejekce štěpu imunologie   patologie   MeSH
• transplantace plic * MeSH
• zvířata MeSH
• Check Tag
• krysa rodu rattus MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

Pattern-recognition receptors (PRRs) recognize pathogen-associated molecular patterns and play an important role in triggering innate immune responses. PRRs distribution and function is well documented in mice and humans, but studies in pigs are scarce. Salmonella enterica serovar Typhimurium is common pathogen found in pigs and was used as a model for interaction with PRRs. This study investigated expression of PRRs in porcine leukocyte subpopulations at the mRNA level. Eight subpopulations of leukocytes comprising NK cells, Th, Tc, double positive T cells and γδ T cells, B cells, monocytes and neutrophils were sorted, and the expression of 12 PRRs was measured, including selected Toll-like receptors and their co-receptors, NOD-like receptor NOD2, RP-105, CD14, and dectin. The highest expression rates of most PRRs were observed in monocytes and neutrophils. The B cells expressed high levels of TLR1, TLR6, TLR9, TLR10, and RP-105. Only monocytes and γδ T cells were found to respond to Salmonella enterica serovar Typhimurium infection by intensification of PRRs expression. In Th and B cells, PRRs mRNA down-regulation was detected after infection.

• MeSH
• down regulace MeSH
• leukocyty metabolismus   mikrobiologie   MeSH
• messenger RNA genetika   MeSH
• neutrofily metabolismus   MeSH
• prasata MeSH
• přirozená imunita MeSH
• receptory rozpoznávající vzory genetika   metabolismus   MeSH
• regulace genové exprese imunologie   MeSH
• Salmonella typhimurium fyziologie   MeSH
• salmonelová infekce u zvířat imunologie   MeSH
• séroskupina MeSH
• T-lymfocyty metabolismus   MeSH
• toll-like receptory genetika   metabolismus   MeSH
• zvířata MeSH
• Check Tag
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

Interleukin-2 (IL-2) is a pleiotropic cytokine that regulates immune cell homeostasis and has been used to treat a range of disorders including cancer and autoimmune disease. IL-2 signals via interleukin-2 receptor-β (IL-2Rβ):IL-2Rγ heterodimers on cells expressing high (regulatory T cells, Treg) or low (effector cells) amounts of IL-2Rα (CD25). When complexed with IL-2, certain anti-cytokine antibodies preferentially stimulate expansion of Treg (JES6-1) or effector (S4B6) cells, offering a strategy for targeted disease therapy. We found that JES6-1 sterically blocked the IL-2:IL-2Rβ and IL-2:IL-2Rγ interactions, but also allosterically lowered the IL-2:IL-2Rα affinity through a "triggered exchange" mechanism favoring IL-2Rα(hi) Treg cells, creating a positive feedback loop for IL-2Rα(hi) cell activation. Conversely, S4B6 sterically blocked the IL-2:IL-2Rα interaction, while also conformationally stabilizing the IL-2:IL-2Rβ interaction, thus stimulating all IL-2-responsive immune cells, particularly IL-2Rβ(hi) effector cells. These insights provide a molecular blueprint for engineering selectively potentiating therapeutic antibodies.

• MeSH
• autoimunitní nemoci imunologie   MeSH
• interleukin-2 chemie   genetika   imunologie   metabolismus   MeSH
• kompetitivní vazba účinky léků   MeSH
• lidé MeSH
• molekulární modely * MeSH
• myši inbrední BALB C MeSH
• myši MeSH
• progrese nemoci MeSH
• proliferace buněk účinky léků   MeSH
• protilátky chemie   imunologie   farmakologie   MeSH
• průtoková cytometrie MeSH
• regulace genové exprese imunologie   MeSH
• regulační T-lymfocyty cytologie   účinky léků   imunologie   MeSH
• signální transdukce účinky léků   MeSH
• T-lymfocyty - podskupiny cytologie   účinky léků   imunologie   MeSH
• terciární struktura proteinů MeSH
• vazba proteinů účinky léků   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Research Support, N.I.H., Extramural MeSH

Účel přehledu: MikroRNA (miRNA) moduluje genovou transkripci při reakci na stresory vnějšího prostředí a další podněty. Význam miRNA při zánětu a pro imunitu již byl prokázán a další důkazy naznačují, že miRNA hraje úlohu také při alergickém astmatu. Nové poznatky: Byly publikovány studie zkoumající expresi miRNA v biologických tekutinách pacientů s astmatem a kontrolních osob a bylo zjištěno, že hraje roli ve skupinách imunitních buněk. Bylo řešeno také budoucí využití miRNA v léčbě. miRNA‑146a se podílí na autoimunitním procesu a alergickém zánětu a miRNA‑155 na vzniku atopie. Zacílení miRNA‑1 a miRNA‑145 bylo použito k inhibici plicního zánětu u myší s astmatem. Ačkoli je třeba tyto nové poznatky ještě potvrdit, mohla by být miRNA užitečným biomarkerem onemocnění. Její léčebné využití však stále není jasné. Souhrn: Existuje možnost využití cirkulující miRNA jako biomarkeru stavu onemocnění nebo odpovědi na léčbu. Využití miRNA v léčbě astmatu zůstává zatím nedořešené.

• MeSH
• biologické markery MeSH
• bronchiální astma * imunologie   patologie   terapie   MeSH
• lidé MeSH
• mikro RNA * imunologie   MeSH
• myši MeSH
• plíce * imunologie   patologie   MeSH
• regulace genové exprese * imunologie   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• myši MeSH
• zvířata MeSH
• Publikační typ
• přehledy MeSH

The expression of the main cytochrome P450 enzyme CYP3A4 displays enormous interindividual variability. Studies addressing the genetic variability of either the CYP3A4 gene itself or its key transcription factors have not found any crucial polymorphism contributing to this variability in expression, a phenomenon is referred to as the “missing heritability of CYP3A4 variability.” Several reports have recently described microRNAs (miRNAs) targeting the CYP3A4 gene and/or its major transcription factors. A comprehensive bioinformatic analysis was performed using the miRDB, PITA, miRanda and TargetScan programs in the search for hypothetical miRNAs targeting 3′-untranslated regions of PXR, CAR, VDR, HNF4α, RXRα, SHP and GRα genes controlling CYP3A4 expression. We propose several novel miRNAs identified parallelly by at least three algorithms to the target analyzed genes. In particular, we found novel promising miRNAs which may be involved in the indirect PXR-mediated CYP3A4 gene expression such as miR-18a and miR-18b, miR-449a, miR-449b and miR-34a. We also hypothesize that some miRNAs may play the role of a master regulator of NRs since they are predicted to target more than three genes. The identification of miRNAs determining CYP3A4 interindividual variability might be an important step toward progress in pharmacogenetics and personalized medicine.

• Klíčová slova
• jaderné receptory regulující expresi genu CYP3A4,
• MeSH
• biotransformace genetika   imunologie   účinky léků   MeSH
• cytochrom P-450 CYP3A farmakologie   genetika   účinky léků   MeSH
• farmakogenetika metody   trendy   MeSH
• genetický výzkum MeSH
• individualizovaná medicína metody   trendy   MeSH
• lidé MeSH
• mikro RNA * farmakologie   genetika   imunologie   MeSH
• regulace genové exprese * genetika   imunologie   MeSH
• systém (enzymů) cytochromů P-450 genetika   účinky léků   MeSH
• výpočetní biologie metody   trendy   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• práce podpořená grantem MeSH

• MeSH
• antigen CTLA-4 izolace a purifikace   účinky léků   MeSH
• antigeny CD273 izolace a purifikace   účinky léků   MeSH
• antigeny CD274 izolace a purifikace   účinky léků   MeSH
• antigeny CD279 antagonisté a inhibitory   MeSH
• biologické markery * krev   MeSH
• biopsie metody   využití   MeSH
• cytokiny izolace a purifikace   krev   MeSH
• interferon gama izolace a purifikace   MeSH
• ipilimumab MeSH
• karcinom z renálních buněk * farmakoterapie   sekundární   terapie   MeSH
• klinické zkoušky, fáze I jako téma MeSH
• kongresy jako téma MeSH
• lidé MeSH
• monoklonální protilátky * terapeutické užití   toxicita   účinky léků   MeSH
• nádory ledvin farmakoterapie   sekundární   terapie   MeSH
• nivolumab MeSH
• receptory antigenů T-buněk izolace a purifikace   krev   účinky léků   MeSH
• regulace genové exprese genetika   imunologie   účinky léků   MeSH
• statistika jako téma MeSH
• Check Tag
• lidé MeSH