The interplay among different cells in a tissue is essential for maintaining homeostasis. Although disease states have been traditionally attributed to individual cell types, increasing evidence and new therapeutic options have demonstrated the primary role of multicellular functions to understand health and disease, opening new avenues to understand pathogenesis and develop new treatment strategies. We recently described the cellular composition and dynamics of the human oral mucosa; however, the spatial arrangement of cells is needed to better understand a morphologically complex tissue. Here, we link single-cell RNA sequencing, spatial transcriptomics, and high-resolution multiplex fluorescence in situ hybridisation to characterise human oral mucosa in health and oral chronic inflammatory disease. We deconvolved expression for resolution enhancement of spatial transcriptomic data and defined highly specialised epithelial and stromal compartments describing location-specific immune programs. Furthermore, we spatially mapped a rare pathogenic fibroblast population localised in a highly immunogenic region, responsible for lymphocyte recruitment through CXCL8 and CXCL10 and with a possible role in pathological angiogenesis through ALOX5AP. Collectively, our study provides a comprehensive reference for the study of oral chronic disease pathogenesis.

• Klíčová slova
• cell biology, fibroblast, gingiva, human, immunology, inflammation, oral mucosa, periodontal disease, spatial genomics,
• MeSH
• chemokin CXCL10 genetika   MeSH
• fibroblasty MeSH
• interleukin-8 * metabolismus   MeSH
• lidé MeSH
• lymfocyty MeSH
• stanovení celkové genové exprese * MeSH
• transkriptom * MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• chemokin CXCL10 MeSH
• CXCL10 protein, human MeSH Prohlížeč
• CXCL8 protein, human MeSH Prohlížeč
• interleukin-8 * MeSH

We analyzed gene expression in THP-1 cells exposed to metal-based nanomaterials (NMs) [TiO2 (NM-100), ZnO (NM-110), SiO2 (NM-200), Ag (NM-300 K)]. A functional enrichment analysis of the significant differentially expressed genes (DEGs) identified the key modulated biological processes and pathways. DEGs were used to construct protein-protein interaction networks. NM-110 and NM-300 K induced changes in the expression of genes involved in oxidative and genotoxic stress, immune response, alterations of cell cycle, detoxification of metal ions and regulation of redox-sensitive pathways. Both NMs shared a number of highly connected protein nodes (hubs) including CXCL8, ATF3, HMOX1, and IL1B. NM-200 induced limited transcriptional changes, mostly related to the immune response; however, several hubs (CXCL8, ATF3) were identical with NM-110 and NM-300 K. No effects of NM-100 were observed. Overall, soluble nanomaterials NM-110 and NM-300 K exerted a wide variety of toxic effects, while insoluble NM-200 induced immunotoxicity; NM-100 caused no detectable changes on the gene expression level.

• Klíčová slova
• THP-1 cells, gene expression, metal-based nanoparticles, protein-protein interactions,
• MeSH
• hemoxygenasa-1 MeSH
• interleukin-8 metabolismus   genetika   MeSH
• kovové nanočástice toxicita   MeSH
• lidé MeSH
• mapy interakcí proteinů * účinky léků   MeSH
• nanostruktury toxicita   MeSH
• oxid křemičitý toxicita   MeSH
• oxid zinečnatý toxicita   chemie   MeSH
• stříbro * toxicita   MeSH
• THP-1 buňky MeSH
• titan * toxicita   MeSH
• transkripční faktor ATF3 genetika   metabolismus   MeSH
• transkriptom účinky léků   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• ATF3 protein, human MeSH Prohlížeč
• CXCL8 protein, human MeSH Prohlížeč
• hemoxygenasa-1 MeSH
• HMOX1 protein, human MeSH Prohlížeč
• interleukin-8 MeSH
• oxid křemičitý MeSH
• oxid zinečnatý MeSH
• stříbro * MeSH
• titan * MeSH
• titanium dioxide MeSH Prohlížeč
• transkripční faktor ATF3 MeSH

BACKGROUND: The recognition of active inflammation in the central nervous system (CNS) in the absence of infectious agents is challenging. The present study aimed to determine the diagnostic relevance of five selected chemo/cytokines in the recognition of CNS inflammation and in the context of traditional cerebrospinal fluid (CSF) biomarkers (white blood cell [WBC] counts, oligoclonal bands, protein levels, CSF/serum albumin ratios) and clinical diagnoses. METHODS: C-C and C-X-C motif ligands (CCL2, CXCL8, 10 and 13) and interleukin (IL) 6 levels in the CSF and serum from 37 control and 87 symptomatic children with ten different (mostly noninfectious) inflammatory CNS disorders (16 of which had follow-up samples after recovery) were determined using Luminex multiple bead technology and software. Nonparametric tests were used; p < 0.05 was considered statistically significant. Receiver operating characteristic curves were constructed to analyze controls and 1) all symptomatic samples or 2) symptomatic samples without CSF pleocytosis. RESULTS: Compared with the control CSF samples, levels of all investigated chemo/cytokines were increased in symptomatic CSF samples, and only IL-6 remained elevated in recovery samples (p ≤ 0.001). CSF CXCL-13 levels (> 10.9 pg/mL) were the best individual discriminatory criterion to differentiate neuroinflammation (specificity/sensitivity: 97/72% and 97/61% for samples without pleocytosis), followed by CSF WBC counts (specificity/sensitivity: 97/62%). The clinical utility of the remaining CSF chemo/cytokine levels was determined in descending order of sensitivities corresponding to thresholds that ensured 97% specificity for neuroinflammation in samples without pleocytosis (pg/mL; sensitivity %): IL-6 (3.8; 34), CXCL8 (32; 26), CXCL10 (317; 24) and CCL2 (387; 10). Different diagnosis-related patterns of CSF chemo/cytokines were observed. CONCLUSIONS: The increased CSF level of CXCL13 was the marker with the greatest predictive utility for the general recognition of neuroinflammation among all of the individually investigated biomarkers. The potential clinical utility of chemo/cytokines in the differential diagnosis of neuroinflammatory diseases was identified.

• MeSH
• biologické markery krev   mozkomíšní mok   MeSH
• chemokin CCL2 krev   mozkomíšní mok   MeSH
• chemokin CXCL10 krev   mozkomíšní mok   MeSH
• chemokin CXCL13 krev   mozkomíšní mok   MeSH
• chemokiny krev   mozkomíšní mok   MeSH
• dítě MeSH
• interleukin-6 krev   mozkomíšní mok   MeSH
• interleukin-8 krev   mozkomíšní mok   MeSH
• krevní obraz MeSH
• lidé MeSH
• mladiství MeSH
• nemoci centrálního nervového systému mozkomíšní mok   diagnóza   imunologie   MeSH
• předškolní dítě MeSH
• ROC křivka MeSH
• Check Tag
• dítě MeSH
• lidé MeSH
• mladiství MeSH
• mužské pohlaví MeSH
• předškolní dítě MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• biologické markery MeSH
• CCL2 protein, human MeSH Prohlížeč
• chemokin CCL2 MeSH
• chemokin CXCL10 MeSH
• chemokin CXCL13 MeSH
• chemokiny MeSH
• CXCL10 protein, human MeSH Prohlížeč
• CXCL13 protein, human MeSH Prohlížeč
• CXCL8 protein, human MeSH Prohlížeč
• IL6 protein, human MeSH Prohlížeč
• interleukin-6 MeSH
• interleukin-8 MeSH

BACKGROUND: Human colostrum and milk contain components that influence development. Our aim was to use a protein array to determine the cytokine profile of human lacteal secretions and changes that occur during the early postpartum period. METHODS: We collected 17 samples of colostrum during the first 2 days postpartum and a 2nd group of 5 sets of 2 to 3 sequential colostrum or milk samples (at 20- to 30-h intervals). We analyzed the samples with array membranes consisting of 42 or 79 antibodies directed against cytokines. RESULTS: In most samples, we detected the previously described cytokines interleukin-8 (IL-8)/CXCL8, epidermal growth factor (EGF), growth-related oncoprotein (GRO)/CXCL1-3, angiogenin, transforming growth factor beta-2, and monocyte chemotactic protein 1 (MCP-1/CCL2). In addition, we found 32 cytokines that have not been described before in colostrum. Cytokine concentrations differed among mothers, and the spectrum of cytokines changed with time after delivery. A significant decrease occurred in IL-12 and macrophage inflammatory protein-1delta/CCL15 and a significant increase in MCP-1/CCL2. The production of angiogenin, vascular endothelial growth factor, GRO/CXCL1-3, EGF, and IL-8/CXCL8 remained high throughout. The concentrations of 2 selected cytokines measured with the array technique and ELISA showed moderate to strong correlation (r = 0.63 for EGF and r = 0.84 for IL-8/CXCL8). CONCLUSION: Despite the lack of precise quantification, the protein array might be suitable for cytokine screening. It allows simultaneous detection of a broad spectrum of cytokines (including those not described before) in lacteal secretions.

• MeSH
• časové faktory MeSH
• chemokiny analýza   MeSH
• čipová analýza proteinů MeSH
• cytokiny analýza   MeSH
• dospělí MeSH
• ELISA MeSH
• kolostrum chemie   MeSH
• lidé MeSH
• mateřské mléko chemie   MeSH
• mezibuněčné signální peptidy a proteiny analýza   MeSH
• poporodní období MeSH
• proteomika MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• srovnávací studie MeSH
• Názvy látek
• chemokiny MeSH
• cytokiny MeSH
• mezibuněčné signální peptidy a proteiny MeSH

Interleukin-8 (IL-8, CXCL8) was originally discovered as a powerful attractor and activator of polymorphonuclear leukocytes. It was soon recognized that IL-8 also affects proliferation and migration of cancer cells, tumor angiogenesis and metastasis, and that it is expressed in many cancerous cell types. IL-8 protein expression is usually increased in serum of cancer patients, but markedly higher concentrations are found in cancer-associated non-vascular extracellular fluids, such as pleural effusion, ascites and cyst fluid. Elevated concentrations of IL-8 are indicative of malignant processes also in cerebrospinal fluid, urine, saliva, interstitial fluid and cervicovaginal secretions. Higher IL-8 levels are typically found in high-grade peritumoral fluids rather than low-grade tumors and benign conditions, with the exception of inflammatory processes. In line with recent molecular biology investigations, it appears that the local IL-8 production is related to its malignant origin and to tumor progression. Hence, IL-8 in peritumoral fluid is to be taken into consideration while assessing tumor character and monitoring the tumor progression/remission status. Besides, the data here collected justify the attempts to find an IL-8-targeted inhibitory therapy

• MeSH
• extracelulární tekutina metabolismus   MeSH
• interleukin-8 metabolismus   MeSH
• lidé MeSH
• nádorové biomarkery metabolismus   MeSH
• nádory metabolismus   patologie   MeSH
• prognóza MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH
• Názvy látek
• interleukin-8 MeSH
• nádorové biomarkery MeSH

OBJECTIVE: Adipose tissue-derived factors represent important players in the metabolic regulations acting both on systemic and local level. However, their local concentrations in human adipose tissue are poorly described. METHODS: We measured 24-hour profile and post-glucose load concentrations of selected adipokines in the subcutaneous adipose tissue of 17 healthy women by in vivo microdialysis. During 24-hour period, subjects consumed two standardized meals (at 13.00 h and at 19.00 h). RESULTS: During 24-hour period, fat interleukin-6, interleukin-8/CXCL8, resistin, and hepatocyte growth factor (HGF) exhibited increase/decrease/plateau pattern and peaked at about 14.30 h. Fat leptin exhibited increase/plateau/decrease/increase pattern and reached plateau between 22.00 and 5.30 h. Fat adiponectin exhibited decrease/plateau pattern and reached plateau between 1.00 and 7.00 h. Fat plasminogen activator inhibitor-1 (PAI-1) exhibited decrease/increase pattern with the lowest value at 20.30 h. Oral glucose consumption significantly increased fat adiponectin and resistin levels and decreased fat leptin and PAI-1 levels, respectively. CONCLUSIONS: The levels of studied adipokines in subcutaneous fat exhibited significant variations during the 24-hour period after microdialysis catheter insertion that were not reflected in the circulation. Concentrations of adiponectin, resistin, leptin and PAI-1 were regulated by oral glucose ingestion from 1 to 3 h after oral glucose load in healthy women.

• MeSH
• adipokiny metabolismus   MeSH
• adiponektin metabolismus   MeSH
• glukosa metabolismus   MeSH
• inhibitor aktivátoru plazminogenu 1 metabolismus   MeSH
• interleukin-6 metabolismus   MeSH
• interleukin-8 metabolismus   MeSH
• leptin metabolismus   MeSH
• lidé MeSH
• mikrodialýza metody   MeSH
• mladý dospělý MeSH
• podkožní tuk metabolismus   MeSH
• resistin metabolismus   MeSH
• Check Tag
• lidé MeSH
• mladý dospělý MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• klinické zkoušky MeSH
• práce podpořená grantem MeSH
• Názvy látek
• adipokiny MeSH
• adiponektin MeSH
• glukosa MeSH
• inhibitor aktivátoru plazminogenu 1 MeSH
• interleukin-6 MeSH
• interleukin-8 MeSH
• leptin MeSH
• resistin MeSH

BACKGROUND: Nodular melanoma is one of the most life threatening tumors with still poor therapeutic outcome. Similarly to other tumors, permissive microenvironment is essential for melanoma progression. Features of this microenvironment are arising from molecular crosstalk between the melanoma cells (MC) and the surrounding cell populations in the context of skin tissue. Here, we study the effect of melanoma cells on human primary keratinocytes (HPK). Presence of MC is as an important modulator of the tumor microenvironment and we compare it to the effect of nonmalignant lowly differentiated cells also originating from neural crest (NCSC). METHODS: Comparative morphometrical and immunohistochemical analysis of epidermis surrounding nodular melanoma (n = 100) was performed. Data were compared to results of transcriptome profiling of in vitro models, in which HPK were co-cultured with MC, normal human melanocytes, and NCSC, respectively. Differentially expressed candidate genes were verified by RT-qPCR. Biological activity of candidate proteins was assessed on cultured HPK. RESULTS: Epidermis surrounding nodular melanoma exhibits hyperplastic features in 90% of cases. This hyperplastic region exhibits aberrant suprabasal expression of keratin 14 accompanied by loss of keratin 10. We observe that MC and NCSC are able to increase expression of keratins 8, 14, 19, and vimentin in the co-cultured HPK. This in vitro finding partially correlates with pseudoepitheliomatous hyperplasia observed in melanoma biopsies. We provide evidence of FGF-2, CXCL-1, IL-8, and VEGF-A participation in the activity of melanoma cells on keratinocytes. CONCLUSION: We conclude that the MC are able to influence locally the differentiation pattern of keratinocytes in vivo as well as in vitro. This interaction further highlights the role of intercellular interactions in melanoma. The reciprocal role of activated keratinocytes on biology of melanoma cells shall be verified in the future.

• MeSH
• buněčná diferenciace * genetika   MeSH
• chemokin CXCL1 farmakologie   MeSH
• dospělí MeSH
• epidermální buňky * MeSH
• epidermis patologie   MeSH
• fibroblastový růstový faktor 2 farmakologie   MeSH
• interleukin-8 farmakologie   MeSH
• keratin-10 metabolismus   MeSH
• keratin-14 metabolismus   MeSH
• keratinocyty cytologie   účinky léků   metabolismus   MeSH
• lidé středního věku MeSH
• lidé MeSH
• melanocyty metabolismus   MeSH
• melanom metabolismus   patologie   MeSH
• metastázy nádorů MeSH
• mezibuněčná komunikace * MeSH
• nádorové buněčné linie MeSH
• proteiny S100 metabolismus   MeSH
• senioři MeSH
• stanovení celkové genové exprese MeSH
• vaskulární endoteliální růstový faktor A farmakologie   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• chemokin CXCL1 MeSH
• fibroblastový růstový faktor 2 MeSH
• interleukin-8 MeSH
• keratin-10 MeSH
• keratin-14 MeSH
• proteiny S100 MeSH
• vaskulární endoteliální růstový faktor A MeSH

Proinflammatory cytokines play important roles in the pathogenesis of diseases caused by enterohemorrhagic Escherichia coli (EHEC) O157, but the spectrum of bacterial components involved in the proinflammatory responses is not fully understood. Here, we investigated the abilities of outer membrane vesicles (OMVs), nanoparticles released by EHEC O157 during growth, to induce production of proinflammatory cytokines in human intestinal epithelial cells. OMVs from both EHEC O157:H7 and sorbitol-fermenting (SF) EHEC O157:H- induced production of interleukin-8 (IL-8) in Caco-2, HCT-8, and HT-29 intestinal epithelial cell lines. H7 flagellin was the key IL-8-inducing component of EHEC O157:H7 OMVs, whereas cytolethal distending toxin V and O157 lipopolysaccharide (LPS) largely contributed to IL-8 production elicited by flagellin-lacking OMVs from SF EHEC O157:H-. The H7 flagellin-mediated signaling via Toll-like receptor (TLR) 5, and O157 LPS-mediated signaling via TLR4/MD-2 complex, which were followed by activation of the nuclear factor NF-κB were major pathways underlying IL-8 production induced by EHEC O157 OMVs. The proinflammatory and immunomodulatory capacities of EHEC O157 OMVs have pathogenetic implications and support the OMVs as suitable vaccine candidates.

• Klíčová slova
• Enterohemorrhagic Escherichia coli O157, Flagellin, Immunomodulation, Lipopolysaccharide, Outer membrane vesicles, Proinflammatory cytokines,
• MeSH
• buněčná membrána metabolismus   MeSH
• buňky HT-29 MeSH
• Caco-2 buňky MeSH
• epitelové buňky metabolismus   MeSH
• Escherichia coli O157 patogenita   MeSH
• faktory virulence metabolismus   MeSH
• flagelin metabolismus   MeSH
• infekce vyvolané Escherichia coli mikrobiologie   patologie   MeSH
• interleukin-8 biosyntéza   MeSH
• lidé MeSH
• nádorové buněčné linie MeSH
• NF-kappa B metabolismus   MeSH
• proteiny vnější bakteriální membrány metabolismus   MeSH
• proteiny z Escherichia coli metabolismus   MeSH
• signální transdukce MeSH
• střevní sliznice cytologie   mikrobiologie   patologie   MeSH
• toll-like receptor 4 metabolismus   MeSH
• toll-like receptor 5 metabolismus   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• CXCL8 protein, human MeSH Prohlížeč
• faktory virulence MeSH
• flagelin MeSH
• interleukin-8 MeSH
• NF-kappa B MeSH
• proteiny vnější bakteriální membrány MeSH
• proteiny z Escherichia coli MeSH
• TLR4 protein, human MeSH Prohlížeč
• TLR5 protein, human MeSH Prohlížeč
• toll-like receptor 4 MeSH
• toll-like receptor 5 MeSH

Calorie restriction-induced weight loss is accompanied by profound changes in adipose tissue characteristics. To determine the effect of weight loss on differentiation of preadipocytes and secretory capacity of in vitro differentiated adipocytes, we established cultures of these cells from paired subcutaneous adipose tissue biopsies obtained before and at the end of weight-reducing dietary intervention (DI) in 23 obese women. Based on lipid accumulation and the expression of differentiation markers, in vitro adipogenesis increased after weight loss and it was accompanied by enhanced expression of genes involved in de novo lipogenesis. This effect of weight loss was not driven by changes of peroxisome proliferator-activated receptor γ sensitivity to rosiglitazone. Weight loss also enhanced the expression of adiponectin and leptin while reducing that of monocyte chemoattractant protein 1 and interleukin-8 by cultured adipocytes. Thus, the weight-reducing (DI) increased adipogenic capacity of preadipocytes and shifted their secretion toward lower inflammatory profile. Reprogramming of preadipocytes could represent an adaptation to weight loss leading to partial restoration of preobese adipose tissue traits and thus contribute to the improvement of metabolic status. However, enhanced adipogenesis could also contribute to the unwanted weight regain after initial weight loss.

• MeSH
• adipogeneze genetika   fyziologie   MeSH
• adiponektin metabolismus   MeSH
• chemokin CCL2 metabolismus   MeSH
• cytokiny metabolismus   MeSH
• ELISA MeSH
• hmotnostní úbytek genetika   fyziologie   MeSH
• interleukin-8 metabolismus   MeSH
• kultivované buňky MeSH
• leptin metabolismus   MeSH
• lidé MeSH
• obezita MeSH
• PPAR gama metabolismus   MeSH
• rosiglitazon MeSH
• thiazolidindiony farmakologie   MeSH
• tukové buňky cytologie   MeSH
• Check Tag
• lidé MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• adiponektin MeSH
• chemokin CCL2 MeSH
• cytokiny MeSH
• interleukin-8 MeSH
• leptin MeSH
• PPAR gama MeSH
• rosiglitazon MeSH
• thiazolidindiony MeSH

Kyasanur Forest disease virus (KFDV) is a highly pathogenic tick-borne flavivirus enzootic to India. In humans, KFDV causes a severe febrile disease. In some infected individuals, hemorrhagic manifestations, such as bleeding from the nose and gums and gastrointestinal bleeding with hematemesis and/or blood in the stool, have been reported. However, the mechanisms underlying these hemorrhagic complications remain unknown, and there is no information about the specific target cells for KFDV. We investigated the interaction of KFDV with vascular endothelial cells (ECs) and monocyte-derived dendritic cells (moDCs), which are key targets for several other hemorrhagic viruses. Here, we report that ECs are permissive to KFDV infection, which leads to their activation, as demonstrated by the upregulation of E-selectin, intercellular adhesion molecule 1, and vascular cell adhesion molecule 1 at the mRNA and protein levels. Increased expression of these adhesive molecules correlated with increased leukocyte adhesion. Infected ECs upregulated the expression of interleukin (IL)-6 but not IL-8. Additionally, moDCs were permissive to KFDV infection, leading to increased release of IL-6 and tumor necrosis factor-α. Supernatants from KFDV-infected moDCs caused EC activation, as measured by leukocyte adhesion. The results indicate that ECs and moDCs can be targets for KFDV and that both direct and indirect mechanisms can contribute to EC activation.

• MeSH
• CD antigeny genetika   imunologie   MeSH
• cévní buněčněadhezivní molekula-1 genetika   imunologie   MeSH
• dendritické buňky imunologie   virologie   MeSH
• endoteliální buňky imunologie   virologie   MeSH
• interleukin-6 genetika   imunologie   MeSH
• interleukin-8 genetika   imunologie   MeSH
• kadheriny genetika   imunologie   MeSH
• kultivované buňky MeSH
• lidé MeSH
• messenger RNA MeSH
• mezibuněčná adhezivní molekula-1 genetika   imunologie   MeSH
• nemoc kyasanurského lesa imunologie   MeSH
• TNF-alfa genetika   imunologie   MeSH
• viry klíšťové encefalitidy imunologie   patogenita   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• CD antigeny MeSH
• CDH1 protein, human MeSH Prohlížeč
• cévní buněčněadhezivní molekula-1 MeSH
• CXCL8 protein, human MeSH Prohlížeč
• ICAM1 protein, human MeSH Prohlížeč
• IL6 protein, human MeSH Prohlížeč
• interleukin-6 MeSH
• interleukin-8 MeSH
• kadheriny MeSH
• messenger RNA MeSH
• mezibuněčná adhezivní molekula-1 MeSH
• TNF-alfa MeSH