Sarcoidosis is an inflammatory granulomatous disease with unknown etiology driven by cytokines and chemokines. There is limited information regarding the regulation of cytokine/chemokine-receptor network in bronchoalveolar lavage (BAL) cells in pulmonary sarcoidosis, suggesting contribution of miRNAs and transcription factors. We therefore investigated gene expression of 25 inflammation-related miRNAs, 27 cytokines/chemokines/receptors, and a Th1-transcription factor T-bet in unseparated BAL cells obtained from 48 sarcoidosis patients and 14 control subjects using quantitative RT-PCR. We then examined both miRNA-mRNA expressions to enrich relevant relationships. This first study on miRNAs in sarcoid BAL cells detected deregulation of miR-146a, miR-150, miR-202, miR-204, and miR-222 expression comparing to controls. Subanalysis revealed higher number of miR-155, let-7c transcripts in progressing (n = 20) comparing to regressing (n = 28) disease as assessed by 2-year follow-up. Correlation network analysis revealed relationships between microRNAs, transcription factor T-bet, and deregulated cytokine/chemokine-receptor network in sarcoid BAL cells. Furthermore, T-bet showed more pronounced regulatory capability to sarcoidosis-associated cytokines/chemokines/receptors than miRNAs, which may function rather as "fine-tuners" of cytokine/chemokine expression. Our correlation network study implies contribution of both microRNAs and Th1-transcription factor T-bet to the regulation of cytokine/chemokine-receptor network in BAL cells in sarcoidosis. Functional studies are needed to confirm biological relevance of the obtained relationships.

• MeSH
• dospělí MeSH
• genové regulační sítě * MeSH
• lidé středního věku MeSH
• lidé MeSH
• messenger RNA analýza   MeSH
• mikro RNA fyziologie   MeSH
• plicní sarkoidóza imunologie   MeSH
• proteiny T-boxu fyziologie   MeSH
• receptory chemokinů genetika   MeSH
• receptory cytokinové genetika   MeSH
• senioři 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

Monocytes play an essential role in the defense against bacterial pathogens. Bone marrow (BM) and peripheral blood (PB) monocytes in pigs consist of the main "steady-state" subpopulations: CD14 hi/CD163-/SLA-DR- and CD14 low/CD163+/SLA-DR+. During inflammation, the subpopulation of "inflammatory" monocytes expressing very high levels of CD163, but lacking the SLA-DR molecule (being CD14 low/CD163+/SLA-DR-) appears in the BM and PB and replaces the CD14 low/CD163+/SLA-DR+ subpopulation. However, current knowledge of monocyte migration into inflamed tissues in pigs is limited. The aim of the present study was to evaluate the distribution of "inflammatory" CD14 low/CD163+/SLA-DR- monocytes during experimental inflammation induced by Actinobacillus pleuropneumoniae (APP) and a possible role for chemokines in attracting "inflammatory" CD14 low/CD163+/SLA-DR- monocytes into the tissues. Monocyte subpopulations were detected by flow cytometry. Chemokines and chemokine receptors were detected by RT-qPCR. The "steady-state" monocytes were found in the BM, PB, spleen and lungs of control pigs. After APP-infection, "inflammatory" monocytes replaced the "steady-state" subpopulation in BM, PB, spleen and moreover, they appeared in an unaffected area, demarcation zone and necrotic area of the lungs and in tracheobronchial lymph nodes. They did not appear in mesenteric lymph nodes. Levels of mRNA for various chemokines with their appropriate receptors were found to be elevated in BM (CCL3-CCR1/CCR5, CCL8-CCR2/CCR5, CCL19-CCR7), necrotic area of the lungs (CCL3-CCR1, CCL5-CCR1/CCR3, CCL11-CCR3, CCL22/CCR4) and tracheobronchial lymph nodes (CCL3-CCR1) and therefore they could play a role in attracting monocytes into inflamed tissues. In conclusion, "inflammatory" monocytes appear in different lymphoid tissues and the lungs after APP infection in pigs. Various chemokines could drive this process.

• MeSH
• Actinobacillus pleuropneumoniae fyziologie   MeSH
• antigeny diferenciační myelomonocytární metabolismus   MeSH
• CD antigeny metabolismus   MeSH
• chemokiny genetika   metabolismus   MeSH
• infekce bakteriemi rodu Actinobacillus imunologie   mikrobiologie   veterinární   MeSH
• lymfoidní tkáň metabolismus   MeSH
• messenger RNA genetika   MeSH
• monocyty cytologie   metabolismus   MeSH
• nemoci prasat imunologie   mikrobiologie   MeSH
• plíce metabolismus   MeSH
• prasata MeSH
• průtoková cytometrie veterinární   MeSH
• receptory buněčného povrchu metabolismus   MeSH
• receptory chemokinů genetika   metabolismus   MeSH
• zánět mikrobiologie   MeSH
• zvířata MeSH
• Check Tag
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

Upregulation of genes for interferon (IFN)-γ and CXC chemokine receptor (CXCR)3 expression, two crucial molecules in sarcoid inflammation and granuloma formation, is directly controlled by the T-helper (Th)1 transcription factor T-bet (T-box, expressed in T-cells). However, there is no information on T-bet expression in sarcoidosis or its relationship with "sarcoidosis-associated" genes. Therefore, we investigated expression of T-bet mRNA and, in parallel, a spectrum of genes known to be involved in sarcoidosis pathogenesis. Transcripts were determined in bronchoalveolar lavage (BAL) cells from 62 sarcoidosis patients and 25 controls by quantitative RT-PCR; T-bet protein was localised by immunohistochemistry. Patient's BAL cells expressed higher mRNA T-bet levels than those of controls (mean ± sd fold change 3.64 ± 1.72; p = 0.00006). T-bet mRNA expression did not vary between clinical phenotypes as assessed by chest radiography stage, presence/absence of Löfgren's syndrome, extrapulmonary/pulmonary involvement or progressing/remitting disease (p > 0.05). T-bet mRNA expression correlated with expression of IFN-γ, CC chemokine ligand 5, CXC chemokine ligand (CXC)10, interleukin (IL)-2 receptor/IL-15 receptor β, CXCR3 and CXCR6 (p < 0.01). T-bet protein was localised to alveolar macrophages and lymphocytes, tissue multinucleated giant cells, macrophages and lymphocytes. In pulmonary sarcoidosis, T-bet upregulation is associated with changes in expression of IFN-γ, CXCR3 and chemokines/receptors involved in the pathogenesis of sarcoidosis, which suggests a role for T-bet in this Th1 disease, including modulation of some sarcoidosis-associated genes.

• MeSH
• bronchoalveolární lavážní tekutina chemie   cytologie   MeSH
• chemokin CCL5 genetika   metabolismus   MeSH
• dospělí MeSH
• exprese genu MeSH
• interferon gama genetika   metabolismus   MeSH
• lidé středního věku MeSH
• lidé MeSH
• lymfatické uzliny metabolismus   MeSH
• messenger RNA metabolismus   MeSH
• plíce metabolismus   MeSH
• plicní sarkoidóza genetika   imunologie   metabolismus   MeSH
• proteiny T-boxu metabolismus   MeSH
• receptory chemokinů genetika   metabolismus   MeSH
• receptory CXCR3 genetika   metabolismus   MeSH
• receptory interleukinu-2 genetika   metabolismus   MeSH
• Th1 buňky imunologie   metabolismus   MeSH
• upregulace MeSH
• virové receptory genetika   metabolismus   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

CONTEXT: Low-grade inflammation links obesity, type 2 diabetes mellitus (T2DM), and cardiovascular diseases. OBJECTIVE: To explore the expression profile of genes involved in inflammatory pathways in adipose tissue and peripheral monocytes (PM) of obese patients with and without T2DM at baseline and after dietary intervention. DESIGN: Two-week intervention study with very-low-calorie diet (VLCD). SETTING: University hospital. Patients: Twelve obese females with T2DM, 8 obese nondiabetic females (OB) and 15 healthy age-matched females. INTERVENTION: Two weeks of VLCD (2500 kJ/d). MAIN OUTCOME MEASURES: Metabolic parameters, circulating cytokines, hormones, and mRNA expression of 39 genes in sc adipose tissue (SCAT) and PM. RESULTS: Both T2DM and OB group had significantly increased serum concentrations of circulating proinflammatory factors (C-reactive protein, TNFα, IL-6, IL-8), mRNA expression of macrophage antigen CD68 and proinflammatory chemokines (CCL-2, -3, -7, -8, -17, -22) in SCAT and complementary chemokine receptors (CCR-1, -2, -3, -5) and other proinflammatory receptors (toll-like receptor 2 and 4, TNF receptor superfamily 1A and 1B, IL-6R) in PM, with OB group showing less pronounced chemoattracting and proinflammatory profile compared to T2DM group. In T2DM patients VLCD decreased body weight, improved metabolic profile, and decreased mRNA expression of up-regulated CCRs in PM and chemokines [CCL 8, chemokine (C-X-C motif) ligand 10] in SCAT. VLCD markedly increased mRNA expression of T-lymphocyte attracting chemokine CCL-17 in SCAT. CONCLUSION: Obese patients with and without T2DM have increased mRNA expression of chemotactic and proinflammatory factors in SCAT and expression of corresponding receptors in PM. Two weeks of VLCD significantly improved this profile in T2DM patients.

• MeSH
• adipokiny genetika   metabolismus   MeSH
• chemokiny genetika   metabolismus   MeSH
• diabetes mellitus 2. typu krev   komplikace   dietoterapie   genetika   MeSH
• kalorická restrikce MeSH
• lidé středního věku MeSH
• lidé MeSH
• mediátory zánětu metabolismus   MeSH
• messenger RNA genetika   metabolismus   MeSH
• monocyty metabolismus   MeSH
• obezita krev   komplikace   dietoterapie   genetika   MeSH
• podkožní tuk metabolismus   MeSH
• receptory adipokinů genetika   metabolismus   MeSH
• receptory chemokinů genetika   metabolismus   MeSH
• redukční dieta MeSH
• regulace genové exprese MeSH
• zánět komplikace   genetika   metabolismus   MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• klinické zkoušky kontrolované MeSH
• práce podpořená grantem MeSH

Differences in biological responses to exposure to hazardous airborne substances between children and adults have been reported, suggesting children to be more susceptible. Aim of this study was to improve our understanding of differences in susceptibility in cancer risk associated with air pollution by comparing genome-wide gene expression profiles in peripheral blood of children and their parents. Gene expression analysis was performed in blood from children and parents living in two different regions in the Czech Republic with different levels of air pollution. Data were analyzed by two different approaches: one method first selected significantly differentially expressed genes and analyzed these gene lists for overrepresented biological processes, whereas the other applied the T-profiler tool to directly perform pathway analyses on the total gene set without preselection of significantly modulated gene expressions. In addition, gene expressions in both children and adults were investigated for associations with micronuclei frequencies. Both analysis approaches returned considerably more genes or gene groups and pathways that significantly differed between children from both regions than between parents. Very little overlap was observed between children and adults. The two most important biological processes or molecular functions significantly modulated in children, but not in adults, are nucleosome and immune response related. Our study suggests differences between children and adults in relation to air pollution exposure at the transcriptome level. The findings underline the necessity of implementing environmental health policy measures specifically for protecting children's health.

• MeSH
• dítě MeSH
• dospělí MeSH
• genetická predispozice k nemoci * MeSH
• lidé MeSH
• nukleární rodina MeSH
• receptory chemokinů genetika   MeSH
• regulace genové exprese MeSH
• RNA genetika   MeSH
• rodiče MeSH
• sestřih RNA genetika   MeSH
• stanovení celkové genové exprese * MeSH
• znečištění ovzduší * MeSH
• Check Tag
• dítě MeSH
• dospělí MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• multicentrická studie MeSH
• práce podpořená grantem MeSH
• Geografické názvy
• Česká republika MeSH

OBJECTIVE: CCX CKR is a decoy chemokine receptor that specifically binds the chemokines CCL19, CCL25 and CCL21. CCL19 was previously found to be upregulated in pulmonary sarcoidosis. We have, therefore, investigated CCX CKR expression in this inflammatory disease. METHODS AND RESULTS: CCX CKR mRNA was semiquantitated using RT-PCR in unseparated bronchoalveolar (BAL) cells from sarcoidosis patients (S, n = 29) and healthy control subjects (C, n = 9). CCX CKR transcripts were upregulated in patients (mean +/- SEM); S, 0.82 +/- 0.10; C, 0.44 +/- 0.04; p = 0.01; this upregulation paralleled the disease course as assessed by the chest radiographic stage (p < 0.02). Immunocytochemistry localised the CCX CKR protein to ciliated bronchial cells. Flow cytometric fluorescent ligand uptake assay showed that these cells are able to internalize its ligand. CONCLUSION: These observations implicate CCX CKR in the modulation of the inflammatory response in sarcoidosis.

• MeSH
• bronchoalveolární lavážní tekutina * cytologie   chemie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• messenger RNA biosyntéza   MeSH
• plicní sarkoidóza imunologie   metabolismus   MeSH
• počet leukocytů MeSH
• receptory CCR MeSH
• receptory chemokinů * biosyntéza   genetika   MeSH
• upregulace MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• práce podpořená grantem MeSH

• MeSH
• dospělí MeSH
• finanční podpora výzkumu jako téma MeSH
• hodnocení rizik MeSH
• infarkt myokardu genetika   MeSH
• lidé MeSH
• nemoci koronárních tepen genetika   MeSH
• polymerázová řetězová reakce MeSH
• polymorfismus genetický MeSH
• populační charakteristiky MeSH
• receptory chemokinů genetika   MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH

• MeSH
• chemokiny CC fyziologie   genetika   MeSH
• finanční podpora výzkumu jako téma MeSH
• lidé MeSH
• měření bolesti MeSH
• polymorfismus genetický MeSH
• pooperační bolest genetika   MeSH
• receptory chemokinů fyziologie   genetika   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• kongresy MeSH
• srovnávací studie MeSH

• MeSH
• genetická predispozice k nemoci MeSH
• genetická variace MeSH
• infarkt myokardu genetika   MeSH
• polymorfismus genetický MeSH
• receptory chemokinů genetika   MeSH

Chemokines mediate their multiple effects by binding to a variety of specific receptors, that comprise a subfamily of rhodopsin-like, 7-transmembrane domain receptors, coupled to G proteins. Some of these receptors serve as coreceptors for HIV, some of them could be expressed as markers for T lymphocyte functional differentiation. This review aims at summarising data on chemokine receptors, their function in vivo, their target cells and it also mentions association of chemokine receptor polymorphisms with human disease.

• MeSH
• buněčná diferenciace fyziologie   MeSH
• lidé MeSH
• ligandy MeSH
• myši knockoutované genetika   MeSH
• myši MeSH
• polymorfismus genetický MeSH
• receptory chemokinů genetika   metabolismus   fyziologie   MeSH
• T-lymfocyty cytologie   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH