Chlamydia psittaci pneumonia (CPP) is a lung disease caused by the infection with the Chla-mydia psittaci bacterium, which can lead to severe acute respiratory distress syndrome and systemic symptoms. This study explored the specific mechanisms underlying the impact of reactive oxygen species (ROS) on the Th17/Treg balance in CPP. The levels of ROS and the differentiation ratio of Th17/Treg in the peripheral blood of healthy individuals and CPP patients were measured using ELISA and flow cytometry, respectively. The association between the ROS levels and Th17/Treg was assessed using Pearson correlation analysis. The ROS levels and the Th17/Treg ratio were measured in CD4+ T cells following H2O2 treatment and NLRP3 inhibition. The effects of H2O2 treatment and NLRP3 inhibition on the NLRP3/IL-1β/caspase-1 pathway were observed using immunoblotting. Compared to the healthy group, the CPP group exhibited increased levels of ROS in the peripheral blood, an elevated ratio of Th17 differentiation, and a decreased ratio of Treg differentiation. ROS levels were positively correlated with the Th17 cell proportion but negatively correlated with the Treg cell proportion. The ROS levels and NLRP3/IL-1β/caspase-1 expression were up-regulated in CD4+ T cells after H2O2 treatment. Furthermore, there was an increase in Th17 differentiation and a decrease in Treg differentiation. Conversely, the NLRP3/IL-1β/caspase-1 pathway inhibition reversed the effects of H2O2 treatment, with no significant change in the ROS levels. ROS regulates the Th17/Treg balance in CPP, possibly through the NLRP3/IL-1β/caspase-1 pathway. This study provides a new perspective on the development of immunotherapy for CPP.

• Klíčová slova
• CD4+ T cells, CPP, NLRP3/IL-1β/Caspase-1, ROS, Th17/Treg,
• MeSH
• buněčná diferenciace * účinky léků   MeSH
• buňky Th17 * imunologie   metabolismus   MeSH
• Chlamydophila psittaci * MeSH
• dospělí MeSH
• interleukin-1beta * metabolismus   MeSH
• kaspasa 1 * metabolismus   MeSH
• lidé středního věku MeSH
• lidé MeSH
• peroxid vodíku metabolismus   MeSH
• protein NLRP3 * metabolismus   MeSH
• psitakóza MeSH
• reaktivní formy kyslíku * metabolismus   MeSH
• regulační T-lymfocyty * imunologie   MeSH
• signální transdukce MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• interleukin-1beta * MeSH
• kaspasa 1 * MeSH
• NLRP3 protein, human MeSH Prohlížeč
• peroxid vodíku MeSH
• protein NLRP3 * MeSH
• reaktivní formy kyslíku * MeSH

Caspase-1, as the main pro-inflammatory cysteine protease, was investigated mostly with respect to inflammation-related processes. Interestingly, caspase-1 was identified as being involved in lipid metabolism, which is extremely important for the proper differentiation of chondrocytes. Based on a screening investigation, general caspase inhibition impacts the expression of Cd36 in chondrocytes, the fatty acid translocase with a significant impact on lipid metabolism. However, the engagement of individual caspases in the effect has not yet been identified. Therefore, the hypothesis that caspase-1 might be a candidate here appears challenging. The primary aim of this study thus was to find out whether the inhibition of caspase-1 activity would affect Cd36 expression in a chondrogenic micromass model. The expression of Pparg, a regulator Cd36, was examined as well. In the caspase-1 inhibited samples, both molecules were significantly downregulated. Notably, in the treated group, the formation of the chondrogenic nodules was apparently disrupted, and the subcellular deposition of lipids and polysaccharides showed an abnormal pattern. To further investigate this observation, the samples were subjected to an osteogenic PCR array containing selected markers related to cartilage/bone cell differentiation. Among affected molecules, Bmp7 and Gdf10 showed a significantly increased expression, while Itgam, Mmp9, Vdr, and Rankl decreased. Notably, Rankl is a key marker in bone remodeling/homeostasis and thus is a target in several treatment strategies, including a variety of fatty acids, and is balanced by its decoy receptor Opg (osteoprotegerin). To evaluate the effect of Cd36 downregulation on Rankl and Opg, Cd36 silencing was performed using micromass cultures. After Cd36 silencing, the expression of Rankl was downregulated and Opg upregulated, which was an inverse effect to caspase-1 inhibition (and Cd36 upregulation). These results demonstrate new functions of caspase-1 in chondrocyte differentiation and lipid metabolism-related pathways. The effect on the Rankl/Opg ratio, critical for bone maintenance and pathology, including osteoarthritis, is particularly important here as well.

• Klíčová slova
• Cd36, cartilage, caspase-1, chondrocytes, inhibition, lipid metabolism, osteoarthritis,
• MeSH
• buněčná diferenciace účinky léků   MeSH
• chondrocyty metabolismus   MeSH
• chondrogeneze účinky léků   MeSH
• diferenciační antigeny biosyntéza   MeSH
• inhibitory kaspas farmakologie   MeSH
• kaspasa 1 metabolismus   MeSH
• metabolismus lipidů účinky léků   MeSH
• myši MeSH
• osteogeneze účinky léků   MeSH
• zvířata MeSH
• Check Tag
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• Casp1 protein, mouse MeSH Prohlížeč
• diferenciační antigeny MeSH
• inhibitory kaspas MeSH
• kaspasa 1 MeSH

Prostate cancer cells control energy metabolism by chelating intracellular zinc. Thus, zinc delivery has been a popular therapeutic approach for prostate cancer. Here, we propose the use of the membrane-penetrating peptide Novicidin connected to zinc-Schiff base as a carrier vehicle for the delivery of zinc to prostate cells. Mass spectrometry, electrochemistry and spectrophotometry confirmed the formation/stability of this complex and provided insight regarding the availability of zinc for complex interactions. This delivery system showed minor toxicity in normal PNT1A cells and high potency towards PC3 tumor cells. The complex preferentially penetrated PC3 tumor cells in contrast to confinement to the membranes of PNT1A. Furthermore, zinc uptake was confirmed in both cell lines. Molecular analysis was used to confirm the activation of zinc stress (e.g., ZnT-1) and apoptosis (e.g., CASP-1). Our results strongly suggest that the zinc-Schiff base-Novicidin complex has great potential as a novel anticancer drug.

• MeSH
• antitumorózní látky chemie   farmakologie   terapeutické užití   MeSH
• apoptóza účinky léků   MeSH
• exprese genu účinky léků   MeSH
• fluorescenční mikroskopie MeSH
• kaspasa 1 metabolismus   MeSH
• kationické antimikrobiální peptidy chemie   MeSH
• komplexní sloučeniny chemie   farmakologie   terapeutické užití   MeSH
• lidé MeSH
• molekulární konformace MeSH
• nádorové buněčné linie MeSH
• nádory prostaty farmakoterapie   MeSH
• proteiny přenášející kationty metabolismus   MeSH
• Schiffovy báze chemie   MeSH
• spektrometrie hmotnostní - ionizace laserem za účasti matrice MeSH
• zinek chemie   metabolismus   MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• antitumorózní látky MeSH
• kaspasa 1 MeSH
• kationické antimikrobiální peptidy MeSH
• komplexní sloučeniny MeSH
• novicidin MeSH Prohlížeč
• proteiny přenášející kationty MeSH
• Schiffovy báze MeSH
• SLC30A1 protein, human MeSH Prohlížeč
• zinek MeSH

OBJECTIVE: To determine new data related to the expression of caspase 1, superoxiddismutase and calretinin in the placenta and basal decidua in preeclampsia. MATERIAL AND METHODS: Placental and basal decidua samples from 9 preeclamptic and 9 normotensive controls were analyzed using expressions of caspase 1, superoxiddismutase and calretinin assessed by immunohistochemistry. RESULTS: Caspase 1 was expressed in placental syncythium in preeclampsia constantly, while in the control group the expression was weak or absent. In Langhans cells, in fetal sinusoidal capillary endothelia and in Hofbauer cells the expression was equal in both groups. Stronger expression was observed in stromal myofibroblasts in preeclampsia. In preeclampsia, expression of superoxiddismutase in syncythium, in Langhans cells and in decidual cells was weaker. Calretinin was not found in any placental structure. Sporadically, calretinin was expressed in the interstitial extravillous trophoblast cells, in decidual cells and in spiral arterioles in preeclampsia. CONCLUSION: The obtained morphological data correlating with some clinical and biochemical features contribute to understanding of the molecular background of preeclampsia etiopathogenesis.

• MeSH
• decidua metabolismus   MeSH
• dospělí MeSH
• kalbindin 2 MeSH
• kaspasa 1 metabolismus   MeSH
• lidé MeSH
• placenta metabolismus   MeSH
• preeklampsie metabolismus   MeSH
• S100 kalcium vázající protein G metabolismus   MeSH
• superoxiddismutasa metabolismus   MeSH
• těhotenství MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• těhotenství MeSH
• ženské pohlaví MeSH
• Publikační typ
• anglický abstrakt MeSH
• časopisecké články MeSH
• Názvy látek
• CALB2 protein, human MeSH Prohlížeč
• kalbindin 2 MeSH
• kaspasa 1 MeSH
• S100 kalcium vázající protein G MeSH
• superoxiddismutasa MeSH

The multifunctional cytokine interleukin-18 (IL-18) is an important mediator in intestinal inflammatory processes. The aim of this study was to evaluate the constitutive expression of IL-18 and its receptors (IL-18Ralpha and IL-18Rbeta) in intestinal epithelial cells (IEC) stimulated by tumor necrosis factor-alpha (TNF-alpha) and interferon-gamma (IFN-gamma). In addition, cellular proliferation and evaluation of brush border enzymes as differentiation markers were studied. Nontransformed rat intestinal epithelial IEC-6 cells were grown on an extracellular matrix (ECM) in medium with or without TNF-alpha, IFN-gamma, or a combination of both. Gene expression of IL-18, its receptors and apoptotic markers was evaluated using real-time PCR. Expression of IL-18Ralpha protein was demonstrated by flow cytometry and Western blot. Enzymatic activities of brush border enzymes and caspase-1 were determined. The constitutive expression of IL-18, IL-18Ralpha and IL-18Rbeta mRNAs and proteins were detected in IEC-6 cells. The biologically active form of IL-18 was released in response to TNF-alpha and IFN-gamma treatment. Exogenous IL-18 had no effect on cellular proliferation, brush border enzyme activities, and gene expression of apoptotic markers. However, the addition of IL-18 stimulated production and release of the chemokine IL-8. These data suggest that IEC-6 cells may be not only a source of IL-18 but also a target for its action.

• MeSH
• apoptóza účinky léků   MeSH
• biologické markery metabolismus   MeSH
• buněčná diferenciace účinky léků   MeSH
• buněčná membrána účinky léků   metabolismus   MeSH
• buněčné linie MeSH
• chemokin CCL2 metabolismus   MeSH
• epitelové buňky cytologie   účinky léků   enzymologie   metabolismus   MeSH
• interferon gama farmakologie   MeSH
• interleukin-18 genetika   metabolismus   MeSH
• kaspasa 1 metabolismus   MeSH
• krysa rodu Rattus MeSH
• kultivační média MeSH
• messenger RNA genetika   metabolismus   MeSH
• počet buněk MeSH
• polymerázová řetězová reakce s reverzní transkripcí MeSH
• receptor interleukinu-18 - alfa-podjednotka genetika   metabolismus   MeSH
• receptor interleukinu-18 - beta-podjednotka genetika   metabolismus   MeSH
• regulace genové exprese účinky léků   MeSH
• střeva cytologie   MeSH
• TNF-alfa farmakologie   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Research Support, N.I.H., Extramural MeSH
• Názvy látek
• biologické markery MeSH
• chemokin CCL2 MeSH
• interferon gama MeSH
• interleukin-18 MeSH
• kaspasa 1 MeSH
• kultivační média MeSH
• messenger RNA MeSH
• receptor interleukinu-18 - alfa-podjednotka MeSH
• receptor interleukinu-18 - beta-podjednotka MeSH
• TNF-alfa MeSH

The effects of isopentenyladenosine (iPA) on tobacco (Nicotiana tabacum L.) BY-2 cells were examined. The number of BY-2 cells decreased in a time- and concentration-dependent manner after being exposed to micromolar concentrations of iPA. This decrease was mainly due to a loss of cell viability, since no substantial changes in cell cycle progression were revealed by flow-cytometric analysis. Dying cells exhibited the typical morphological and biochemical hallmarks of apoptosis, including cell shrinkage, chromatin condensation, and degradation of nuclear DNA to nucleosomal size fragments. Caspase-1-like and caspase-3-like proteases also became activated, the former being dominant. Inhibitor-sensitivity studies revealed that although synthetic caspase inhibitors failed to prevent cell death they markedly reduced cell death in tobacco BY-2 cells, Nu-benzyloxycarbonyl-Val-Ala-Asp-fluoromethylketone, a specific inhibitor for caspase-1, being the most effective. Our results indicate that caspase-like proteases, and particularly caspase-1-like protease, might be critically implicated in iPA-induced apoptosis of BY-2 cells. Finally, the outcome of inhibiting adenosine kinase by 4-amino-3-iodo-1(beta- D-ribofuranosyl)pyrazolo[3,4-d]-pyrimidine revealed that intracellular phosphorylation of iPA is required for its cytotoxicity to develop.

• MeSH
• aktivace enzymů účinky léků   MeSH
• apoptóza účinky léků   MeSH
• chloromethylketony aminokyselin farmakologie   MeSH
• cytokininy farmakologie   MeSH
• endopeptidasy metabolismus   MeSH
• inhibitory kaspas MeSH
• isopentenyladenosin farmakologie   MeSH
• kaspasa 1 metabolismus   MeSH
• kaspasa 3 MeSH
• kaspasy metabolismus   MeSH
• kultivované buňky MeSH
• oligopeptidy farmakologie   MeSH
• regulátory růstu rostlin farmakologie   MeSH
• tabák cytologie   účinky léků   metabolismus   MeSH
• vztah mezi dávkou a účinkem léčiva MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• benzoylcarbonyl-aspartyl-glutamyl-valyl-aspartyl-fluoromethyl ketone MeSH Prohlížeč
• benzyloxycarbonylvalyl-alanyl-aspartyl fluoromethyl ketone MeSH Prohlížeč
• chloromethylketony aminokyselin MeSH
• cytokininy MeSH
• endopeptidasy MeSH
• inhibitory kaspas MeSH
• isopentenyladenosin MeSH
• kaspasa 1 MeSH
• kaspasa 3 MeSH
• kaspasy MeSH
• oligopeptidy MeSH
• regulátory růstu rostlin MeSH