Dysregulation of extracellular matrix (ECM) homeostasis plays a pivotal role in the accelerated degradation of cartilage, presenting a notable challenge for effective osteoarthritis (OA) treatment and cartilage regeneration. In this study, we introduced an injectable hydrogel based on streamlined-zinc oxide (ZnO), which is responsive to matrix metallopeptidase (MMP), for the delivery of miR-17-5p. This approach aimed to address cartilage damage by regulating ECM homeostasis. The ZnO/miR-17-5p composite functions by releasing zinc ions to attract native bone marrow mesenchymal stem cells, thereby fostering ECM synthesis through the proliferation of new chondrocytes. Concurrently, sustained delivery of miR-17-5p targets enzymes responsible for matrix degradation, thereby mitigating the catabolic process. Notably, the unique structure of the streamlined ZnO nanoparticles is distinct from their conventional spherical counterparts, which not only optimizes the rheological and mechanical properties of the hydrogels, but also enhances the efficiency of miR-17-5p transfection. Our male rat model demonstrated that the combination of streamlined ZnO, MMP-responsive hydrogels, and miRNA-based therapy effectively managed the equilibrium between catabolism and anabolism within the ECM, presenting a fresh perspective in the realm of OA treatment.

• MeSH
• buněčná diferenciace * účinky léků   MeSH
• chondrocyty metabolismus   účinky léků   cytologie   MeSH
• chrupavka * účinky léků   MeSH
• extracelulární matrix * metabolismus   účinky léků   MeSH
• homeostáza účinky léků   MeSH
• hydrogely * chemie   MeSH
• kloubní chrupavka účinky léků   MeSH
• krysa rodu Rattus MeSH
• matrixové metaloproteinasy metabolismus   MeSH
• mezenchymální kmenové buňky cytologie   účinky léků   metabolismus   MeSH
• mikro RNA genetika   metabolismus   MeSH
• osteoartróza terapie   patologie   MeSH
• oxid zinečnatý chemie   MeSH
• potkani Sprague-Dawley MeSH
• regenerace MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• hydrogely * MeSH
• matrixové metaloproteinasy MeSH
• mikro RNA MeSH
• oxid zinečnatý MeSH

OBJECTIVE: Insulin-sensitizing drugs, despite their broad use against type 2 diabetes, can adversely affect bone health, and the mechanisms underlying these side effects remain largely unclear. Here, we investigated the different metabolic effects of a series of thiazolidinediones, including rosiglitazone, pioglitazone, and the second-generation compound MSDC-0602K, on human mesenchymal stem cells (MSCs). METHODS: We developed 13C subcellular metabolomic tracer analysis measuring separate mitochondrial and cytosolic metabolite pools, lipidomic network-based isotopologue models, and bioorthogonal click chemistry, to demonstrate that MSDC-0602K differentially affected bone marrow-derived MSCs (BM-MSCs) and adipose tissue-derived MSCs (AT-MSCs). In BM-MSCs, MSDC-0602K promoted osteoblastic differentiation and suppressed adipogenesis. This effect was clearly distinct from that of the earlier drugs and that on AT-MSCs. RESULTS: Fluxomic data reveal unexpected differences between this drug's effect on MSCs and provide mechanistic insight into the pharmacologic inhibition of mitochondrial pyruvate carrier 1 (MPC). Our study demonstrates that MSDC-0602K retains the capacity to inhibit MPC, akin to rosiglitazone but unlike pioglitazone, enabling the utilization of alternative metabolic pathways. Notably, MSDC-0602K exhibits a limited lipogenic potential compared to both rosiglitazone and pioglitazone, each of which employs a distinct lipogenic strategy. CONCLUSIONS: These findings indicate that the new-generation drugs do not compromise bone structure, offering a safer alternative for treating insulin resistance. Moreover, these results highlight the ability of cell compartment-specific metabolite labeling by click reactions and tracer metabolomics analysis of complex lipids to discover molecular mechanisms within the intersection of carbohydrate and lipid metabolism.

• Klíčová slova
• Adipocyte, Bone marrow, Lipid flux analysis, Mitochondrial pyruvate carrier, Tracer metabolomics,
• MeSH
• adipogeneze * účinky léků   MeSH
• buněčná diferenciace účinky léků   MeSH
• hypoglykemika * farmakologie   MeSH
• kultivované buňky MeSH
• lidé MeSH
• metabolomika metody   MeSH
• mezenchymální kmenové buňky účinky léků   metabolismus   MeSH
• osteogeneze * účinky léků   MeSH
• pioglitazon MeSH
• rosiglitazon farmakologie   MeSH
• thiazolidindiony * farmakologie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• hypoglykemika * MeSH
• pioglitazon MeSH
• rosiglitazon MeSH
• thiazolidindiony * MeSH

BACKGROUND: Cytokine licensing with pro-inflammatory molecules, such as tumour necrosis factor-alpha (TNF-α) and interferon-gamma (IFN-γ), has emerged as a promising strategy to enhance the therapeutic potential of multipotent mesenchymal stromal cells (MSCs). While licensing has demonstrated benefits for immunomodulation, its effects on other key MSC functions, including differentiation and paracrine activity, remain incompletely explored. In this study, we evaluated the transcriptomic, metabolomic, and functional changes induced by short-term TNF-α/IFN-γ priming of Wharton's jelly-derived MSCs (WJ-MSCs). METHODS: WJ-MSCs were expanded and exposed to TNF-α and IFN-γ (10 ng/ml each) for 24 h. Transcriptomic analysis was performed using RNA sequencing to identify differentially expressed genes related to immune modulation and lineage commitment. Metabolomic profiling was conducted using high-resolution mass spectrometry to assess changes in metabolic pathways. Functional assays evaluated the effects of cytokine priming on induced differentiation and growth factor secretion. RESULTS: Cytokine licensing induced notable alterations in gene expression, upregulating pathways linked to immune response, inflammation, and cytokine signalling. However, short-term cytokine treatment significantly attenuated the osteogenic and adipogenic differentiation of MSCs, as evidenced by the reduced expression of RUNX2, ALP, CEBPA, and PPARG. The priming had a negligible effect on EGF, FGF-2, HGF, LIF, and SCF secretion. The production of VEGF-A and VEGF-C was elevated, although the levels remained low. Metabolomic analysis revealed enhanced kynurenine pathway activity, indicative of increased tryptophan catabolism, accompanied by elevated levels of fatty acids and polyamines. CONCLUSIONS: Our findings demonstrate that TNF-α/IFN-γ priming reprograms WJ-MSCs by enhancing their immunomodulatory capacity at the expense of differentiation potential. These results highlight the need for tailored strategies to optimize MSC functionality for specific clinical applications.

• Klíčová slova
• Adipogenic and osteogenic differentiation, Cytokine priming, Metabolomics, Multipotent mesenchymal stromal cells, Secretome, Transcriptomics, Wharton’s jelly,
• MeSH
• buněčná diferenciace * účinky léků   MeSH
• cytokiny * farmakologie   MeSH
• imunomodulace * účinky léků   MeSH
• interferon gama * farmakologie   MeSH
• kultivované buňky MeSH
• lidé MeSH
• mezenchymální kmenové buňky * metabolismus   cytologie   účinky léků   imunologie   MeSH
• TNF-alfa * farmakologie   MeSH
• Whartonův rosol * cytologie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• cytokiny * MeSH
• interferon gama * MeSH
• TNF-alfa * MeSH

Bordetella pertussis infects human upper airways and deploys an array of immunosuppressive virulence factors, among which the adenylate cyclase toxin (CyaA) plays a prominent role in disarming host phagocytes. CyaA binds the complement receptor-3 (CR3 aka αMβ2 integrin CD11b/CD18 or Mac-1) of myeloid cells and delivers into their cytosol an adenylyl cyclase enzyme that hijacks cellular signaling through unregulated conversion of cytosolic ATP to cAMP. We found that the action of as little CyaA as 22 pM (4 ng/mL) blocks macrophage colony-stimulating factor (M-CSF)-driven transition of migratory human CD14+ monocytes into macrophages. Global transcriptional profiling (RNAseq) revealed that exposure of monocytes to 22 pM CyaA for 40 hours in culture with 20 ng/mL of M-CSF led to upregulation of genes that exert negative control of monocyte to macrophage differentiation (e.g., SERPINB2, DLL1, and CSNK1E). The sustained CyaA action yielded downregulation of numerous genes involved in processes crucial for host defense, such as myeloid cell differentiation, chemotaxis of inflammatory cells, antigen presentation, phagocytosis, and bactericidal activities. CyaA-elicited signaling also promoted deacetylation and trimethylation of lysines 9 and 27 of histone 3 (H3K9me3 and H3K27me3) and triggered the formation of transcriptionally repressive heterochromatin patches in the nuclei of CyaA-exposed monocytes. These effects were partly reversed by the G9a methyltransferase inhibitor UNC 0631 and by the pleiotropic HDAC inhibitor Trichostatin-A, revealing that CyaA-elicited epigenetic alterations mediate transcriptional reprogramming of monocytes and play a role in CyaA-triggered block of monocyte differentiation into bactericidal macrophage cells.IMPORTANCETo proliferate on host airway mucosa and evade elimination by patrolling sentinel cells, the whooping cough agent Bordetella pertussis produces a potently immunosubversive adenylate cyclase toxin (CyaA) that blocks opsonophagocytic killing of bacteria by phagocytes like neutrophils and macrophages. Indeed, chemotactic migration of CD14+ monocytes to the infection site and their transition into bactericidal macrophages, thus replenishing the exhausted mucosa-patrolling macrophages, represents one of the key mechanisms of innate immune defense to infection. We show that the cAMP signaling action of CyaA already at a very low toxin concentration triggers massive transcriptional reprogramming of monocytes that is accompanied by chromatin remodeling and epigenetic histone modifications, which block the transition of migratory monocytes into bactericidal macrophage cells. This reveals a novel layer of toxin action-mediated hijacking of functional differentiation of innate immune cells for the sake of mucosal pathogen proliferation and transmission to new hosts.

• Klíčová slova
• Bordetella pertussis, RTX toxins, cyclic AMP, differentiation, epigenetics, macrophages, monocytes,
• MeSH
• adenylátcyklasový toxin * metabolismus   MeSH
• Bordetella pertussis * patogenita   enzymologie   MeSH
• buněčná diferenciace * účinky léků   MeSH
• faktor stimulující kolonie makrofágů MeSH
• kultivované buňky MeSH
• lidé MeSH
• makrofágy * účinky léků   cytologie   MeSH
• monocyty * účinky léků   cytologie   fyziologie   MeSH
• přeprogramování buněk * MeSH
• restrukturace chromatinu * účinky léků   MeSH
• signální transdukce MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• adenylátcyklasový toxin * MeSH
• faktor stimulující kolonie makrofágů MeSH

INTRODUCTION: A critical step preceding the potential biomedical application of nanoparticles is the evaluation of their immunomodulatory effects. Such nanoparticles are expected to enter the bloodstream where they can be recognized and processed by circulating monocytes. Despite the required biocompatibility, this interaction can affect intracellular homeostasis and modulate physiological functions, particularly inflammation. This study focuses on titanium dioxide (TiO2) as an example of relatively low cytotoxic nanoparticles with potential biomedical use and aims to evaluate their possible modulatory effects on the inflammasome-based response in human primary monocytes. METHODS: Monocyte viability, phenotypic changes, and cytokine production were determined after exposure to TiO2 (diameter, 25 nm; P25) alone. In the case of the modulatory effects, we focused on NLRP3 activation. The production of IL-1β and IL-10 was evaluated after (a) simultaneous activation of monocytes with bacterial stimuli muramyl dipeptide (MDP), or lipopolysaccharide (LPS), and TiO2 (co-exposure model), (b) prior activation with TiO2 alone and subsequent exposure to bacterial stimuli MDP or LPS. The differentiation of TiO2-treated monocytes into macrophages and their polarization were also assessed. RESULTS: The selected TiO2 concentration range (30-120 µg/mL) did not induce any significant cytotoxic effects. The highest dose of TiO2 promoted monocyte survival and differentiation into macrophages, with the M2 subset being the most prevalent. Nanoparticles alone did not induce substantial production of inflammatory cytokines IL-1β, IL-6, or TNF-α. The immunomodulatory effect on NLRP3 depended on the type of costimulant used. While co-exposure of monocytes to MDP and TiO2 boosted NLRP3 activity, co-exposure to LPS and TiO2 inhibited NLRP3 by enhancing IL-10 release. The inhibitory effect of TiO2 on NLRP3 based on the promotion of IL-10 was confirmed in a post-exposure model for both costimulants. CONCLUSION: This study confirmed a non-negligible modulatory effect on primary monocytes in their inflammasome-based response and differentiation ability.

• Klíčová slova
• NLRP3, TiO2 nanoparticles, immunomodulation, macrophages, monocytes, polarization,
• MeSH
• acetylmuramyl-alanyl-isoglutamin farmakologie   MeSH
• buněčná diferenciace účinky léků   MeSH
• cytokiny metabolismus   MeSH
• inflamasomy účinky léků   imunologie   metabolismus   MeSH
• interleukin-10 metabolismus   MeSH
• interleukin-1beta metabolismus   MeSH
• kovové nanočástice * toxicita   chemie   MeSH
• kultivované buňky MeSH
• lidé MeSH
• lipopolysacharidy farmakologie   MeSH
• makrofágy účinky léků   imunologie   MeSH
• monocyty * účinky léků   imunologie   cytologie   MeSH
• nanočástice * toxicita   chemie   MeSH
• protein NLRP3 metabolismus   MeSH
• testy toxicity metody   MeSH
• titan * toxicita   chemie   farmakologie   MeSH
• viabilita buněk účinky léků   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• acetylmuramyl-alanyl-isoglutamin MeSH
• cytokiny MeSH
• inflamasomy MeSH
• interleukin-10 MeSH
• interleukin-1beta MeSH
• lipopolysacharidy MeSH
• NLRP3 protein, human MeSH Prohlížeč
• protein NLRP3 MeSH
• titan * MeSH
• titanium dioxide MeSH Prohlížeč

In this study, we tested a method for long-term storage of oral mucosal epithelial cells (OMECs) so that the cells could be expanded in vitro after cryopreservation and used for the treatment of bilateral limbal stem cell deficiency. The ability of suspended primary OMECs to proliferate in vitro after cryopreservation was compared to that of OMEC cultures that had undergone the same process. Both were preserved in standard complex medium (COM) with or without cryoprotective agents (CPAs) (gly-cerol at 5 % or 10 % or dimethyl sulphoxide at 10 %). We found that after cryopreservation, primary OMECs could form a confluent cell sheet only in a few samples after 22 ± 2.9 (mean ± SD) days of cultivation with 72.4 % ± 12.9 % overall viability. Instead, all ex vivo OMEC cultures could re-expand after cryopreservation with a comparable viability of 78.6 ± 13.8 %, like primary OMECs, but with significantly faster growth rate (adj. P < 001), forming a confluent cell sheet at 13.7 ± 3.9 days. Gene expression analyses of the ex vivo expansion of OMEC cultures showed that the stemness, proliferation and differentiation-related gene expression was similar before and after cryopreservation, except for KRT13 expres-sion, which significantly decreased after the second passage (adj. P < 0.05). The addition of CPAs had no effect on these outcomes. In conclusion, the optimal strategy for OMEC preservation is to freeze the cells that have been previously cultured, in order to maintain cell viability and the capacity to create a sizable graft even without CPAs.

• Klíčová slova
• cell culture, cryopreservation, cryoprotectives, limbal stem cell deficiency, oral mucosal epithelial cells, stemness,
• MeSH
• buněčná diferenciace účinky léků   MeSH
• časové faktory MeSH
• epitelové buňky * účinky léků   cytologie   metabolismus   MeSH
• kmenové buňky * účinky léků   cytologie   metabolismus   MeSH
• kryoprezervace * metody   MeSH
• kryoprotektivní látky * farmakologie   MeSH
• kultivované buňky MeSH
• lidé MeSH
• proliferace buněk * účinky léků   MeSH
• regulace genové exprese účinky léků   MeSH
• ústní sliznice * cytologie   účinky léků   MeSH
• viabilita buněk účinky léků   MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• kryoprotektivní látky * MeSH

The molecular mechanisms linking obstructive sleep apnea syndrome (OSA) to obesity and the development of metabolic diseases are still poorly understood. The role of hypoxia (a characteristic feature of OSA) in excessive fat accumulation has been proposed. The present study investigated the possible effects of hypoxia (4% oxygen) on de novo lipogenesis by tracking the major carbon sources in differentiating 3T3-L1 adipocytes. Gas-permeable cultuware was employed to cultivate 3T3-L1 adipocytes in hypoxia (4%) for 7 or 14 days of differentiation. We investigated the contribution of glutamine, glucose or acetate using 13C or 14C labelled carbons to the newly synthesized lipid pool, changes in intracellular lipid content after inhibiting citrate- or acetate-dependent pathways and gene expression of involved key enzymes. The results demonstrate that, in differentiating adipocytes, hypoxia decreased the synthesis of lipids from glucose (44.1 ± 8.8 to 27.5 ± 3.0 pmol/mg of protein, p < 0.01) and partially decreased the contribution of glutamine metabolized through the reverse tricarboxylic acid cycle (4.6% ± 0.2-4.2% ± 0.1%, p < 0.01). Conversely, the contribution of acetate, a citrate- and mitochondria-independent source of carbons, increased upon hypoxia (356.5 ± 71.4 to 649.8 ± 117.5 pmol/mg of protein, p < 0.01). Further, inhibiting the citrate- or acetate-dependent pathways decreased the intracellular lipid content by 58% and 73%, respectively (p < 0.01) showing the importance of de novo lipogenesis in hypoxia-exposed adipocytes. Altogether, hypoxia modified the utilization of carbon sources, leading to alterations in de novo lipogenesis in differentiating adipocytes and increased intracellular lipid content.

• MeSH
• acetáty * metabolismus   farmakologie   MeSH
• buněčná diferenciace * účinky léků   MeSH
• buňky 3T3-L1 * MeSH
• citrátový cyklus MeSH
• glukosa * metabolismus   MeSH
• glutamin * metabolismus   MeSH
• hypoxie buňky MeSH
• lipidy biosyntéza   MeSH
• lipogeneze * účinky léků   MeSH
• metabolismus lipidů účinky léků   MeSH
• myši MeSH
• tukové buňky * metabolismus   účinky léků   MeSH
• zvířata MeSH
• Check Tag
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• acetáty * MeSH
• glukosa * MeSH
• glutamin * MeSH
• lipidy MeSH

Inhibition of soluble epoxide hydrolase (sEH) appears to be promising for the treatment of many diseases. Studies have focused on the beneficial effects of epoxyeicosatrienoic acids (EETs), which are sEH substrates. However, our recent studies have shown that the sEH activity is crucial for the proper intestinal cell differentiation. In this recent study, we investigated the impact of TPPU, an inhibitor of sEH, on the colon cancer cell lines Caco2 and HT-29. We analysed the changes in the expression of the cytoskeletal protein ezrin and the phosphorylated protein kinase p38 (p-p38). Our results showed a decrease in ezrin expression in differentiated cells and an increase in p-p38 expression after TPPU treatment. Immunocytochemical staining revealed a higher staining intensity of p-p38 in the nuclei of HT-29 cells following TPPU treatment. Immunohistochemical staining was performed on human samples of normal colon tissue, grade 2 tumours, and embryonal/foetal tissues. The staining intensity of ezrin in tumours was reduced in the surface area compared to the crypts. Additionally, we observed the translocation of p-p38 expression from the cytoplasm to the nucleus during differentiation. The tumour samples exhibited higher levels of p-p38 in the cytoplasm, similar to normal undifferentiated tissue. To observe the disruption of the cytoskeleton after TPPU treatment, confocal microscopy was used. It was found that β-actin associated with ezrin forms clusters under the plasma membranes. All of these results are significant because sEH inhibitors are being tested in clinical trials, but they could cause an unexpected adverse effects.

• Klíčová slova
• Ezrin, Immunohistochemistry, Intestinal Epithelium, P-p38, Soluble Epoxide Hydrolase, TPPU,
• MeSH
• buněčná diferenciace * účinky léků   MeSH
• buňky HT-29 MeSH
• Caco-2 buňky MeSH
• cytoskeletální proteiny * metabolismus   MeSH
• epoxid hydrolasy * antagonisté a inhibitory   metabolismus   MeSH
• fenylmočovinové sloučeniny farmakologie   MeSH
• inhibitory enzymů farmakologie   MeSH
• lidé MeSH
• mitogenem aktivované proteinkinasy p38 metabolismus   MeSH
• nádory tračníku * farmakoterapie   patologie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• cytoskeletální proteiny * MeSH
• epoxid hydrolasy * MeSH
• ezrin MeSH Prohlížeč
• fenylmočovinové sloučeniny MeSH
• inhibitory enzymů MeSH
• mitogenem aktivované proteinkinasy p38 MeSH

Previously, a new biodegradable poly(ester urethane urea) was synthesized based on polycaprolactone-diol and fish gelatin (PU-Gel). In this work, the potential of this new material for neural tissue engineering is evaluated. Membranes with randomly oriented fibers and with aligned fibers are produced using electrospinning and characterized regarding their mechanical behavior under both dry and wet conditions. Wet samples exhibit a lower Young's modulus than dry ones and aligned membranes are stiffer and more brittle than those randomly oriented. Cyclic tensile tests are conducted and high values for recovery ratio and resilience are obtained. Both membranes exhibited a hydrophobic surface, measured by the water contact angle (WCA). Human mesenchymal stem cells from umbilical cord tissue (UC-MSCs) and human neural stem cells (NSCs) are seeded on both types of membranes, which support their adhesion and proliferation. Cells stained for the cytoskeleton and nucleus in membranes with aligned fibers display an elongated morphology following the alignment direction. As the culture time increased, higher cell viability is obtained on randomfibers for UC-MSCs while no differences are observed for NSCs. The membranes support neuronal differentiation of NSCs, as evidenced by markers for a neuronal filament protein (NF70) and for a microtubule-associated protein (MAP2).

• Klíčová slova
• electrospinning, gelatin, mesenchymal stem cells, neural stem cells, poly(ester urethane urea),
• MeSH
• biokompatibilní materiály chemie   farmakologie   MeSH
• buněčná adheze účinky léků   MeSH
• buněčná diferenciace účinky léků   MeSH
• kultivované buňky MeSH
• lidé MeSH
• mezenchymální kmenové buňky * cytologie   účinky léků   metabolismus   MeSH
• nervové kmenové buňky * cytologie   účinky léků   metabolismus   MeSH
• pevnost v tahu MeSH
• polyestery * chemie   farmakologie   MeSH
• polyurethany * chemie   farmakologie   MeSH
• proliferace buněk účinky léků   MeSH
• testování materiálů MeSH
• tkáňové inženýrství * metody   MeSH
• tkáňové podpůrné struktury chemie   MeSH
• viabilita buněk účinky léků   MeSH
• želatina * chemie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• biokompatibilní materiály MeSH
• poly(ester urethane)urea MeSH Prohlížeč
• polyestery * MeSH
• polyurethany * MeSH
• želatina * MeSH

CD8+ T cells are essential for adaptive immunity against infection and tumors. Their ability to proliferate after stimulation is crucial to their functionality. Dendritic cells (DCs) are professional antigen-presenting cells that induce their proliferation. Here, we show that thapsigargin-induced LAD2 mast cell (MC) line-released products can impair the ability of monocyte-derived DCs to induce CD8+ T-cell proliferation and the generation of Th1 cytokine-producing T cells. We found that culture medium conditioned with LAD2 MCs previously stimulated with thapsigargin (thapsLAD2) induces maturation of DCs as determined by the maturation markers CD80, CD83, CD86, and HLA-DR. However, thapsLAD2-matured DCs produced no detectable TNFα or IL-12 during the maturation. In addition, although their surface expression of PD-L1 was comparable with the immature or TLR7/8-agonist (R848)-matured DCs, their TIM-3 expression was significantly higher than in immature DCs and even much higher than in R848-matured DCs. In addition, contrary to R848-matured DCs, the thapsLAD2-matured DCs only tended to induce enhanced proliferation of CD4+ T cells than immature DCs. For CD8+ T cells, this tendency was not even detected because thapsLAD2-matured and immature DCs comparably induced their proliferation, which contrasted with the significantly enhanced proliferation induced by R848-matured DCs. Furthermore, these differences were comparably recapitulated in the ability of the tested DCs to induce IFNγ- and IFNγ/TNFα-producing T cells. These findings show a novel mechanism of MC-mediated regulation of adaptive immune responses.

• MeSH
• aktivace lymfocytů * účinky léků   imunologie   MeSH
• buněčná diferenciace * účinky léků   MeSH
• buněčné linie MeSH
• buněčný receptor 2 viru hepatitidy A metabolismus   MeSH
• CD8-pozitivní T-lymfocyty * imunologie   účinky léků   MeSH
• cytokiny metabolismus   MeSH
• dendritické buňky * imunologie   účinky léků   metabolismus   MeSH
• imidazoly farmakologie   MeSH
• lidé MeSH
• mastocyty * imunologie   účinky léků   metabolismus   MeSH
• monocyty imunologie   účinky léků   metabolismus   MeSH
• proliferace buněk * účinky léků   MeSH
• thapsigargin * farmakologie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• buněčný receptor 2 viru hepatitidy A MeSH
• cytokiny MeSH
• HAVCR2 protein, human MeSH Prohlížeč
• imidazoly MeSH
• thapsigargin * MeSH