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
• transkripční faktor T-bet 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
• messenger RNA MeSH
• mikro RNA MeSH
• proteiny T-boxu MeSH
• receptory chemokinů MeSH
• receptory cytokinové MeSH
• transkripční faktor T-bet MeSH

Recruitment of inflammatory cells to the arterial wall is an important pathogenic mechanism of atherosclerosis and coronary artery disease (CAD). Functional variability in the genes encoding for chemokines that promote infiltration of atherosclerotic plaques by macrophages and lymphocytes may therefore contribute to the genetic susceptibility to CAD. We, therefore, investigated the association between myocardial infarction (MI) and polymorphisms in the promoter regions of the chemokine genes CCL19 and CCL21. Based on re-sequencing screening we selected and, using PCR-SSP, determined three polymorphisms of CCL19 gene (GenBank ID rs2233872) and CCL21 gene (GenBank ID rs11574914 and rs11574915) in 211 Czech patients with MI and 150 healthy control subjects. There was no difference in allelic frequencies of the investigated SNPs between patients and controls (p>0.05). However, the proportion of homozygotes for the minor G allele of the CCL21 promoter variant (rs11574915 GG) was lower among the MI patients (1%) in comparison with the control subjects (5%, nominal p=0.03). Though rare in the Czech population, CCL21 (rs11574915) GG genotype may confer protection from myocardial infarction. Our preliminary data have to be independently replicated.

• MeSH
• alely MeSH
• chemokin CCL19 genetika   MeSH
• chemokin CCL21 genetika   MeSH
• dospělí MeSH
• frekvence genu MeSH
• genetická variace * MeSH
• genetické asociační studie MeSH
• genotyp MeSH
• infarkt myokardu genetika   MeSH
• jednonukleotidový polymorfismus MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladý dospělý MeSH
• promotorové oblasti (genetika) * MeSH
• studie případů a kontrol MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Geografické názvy
• Česká republika MeSH
• Názvy látek
• chemokin CCL19 MeSH
• chemokin CCL21 MeSH

The objective of this study was to assess protein levels for candidate cytokines, chemokines, growth factors, matrix metalloproteinases and their inhibitors in bronchoalveolar lavage fluid (BALF) in patients with polar forms of pulmonary sarcoidosis, i.e. Löfgren's syndrome (LS) and more advanced chest X-ray (CXR) stage III disease. Twenty-four inflammatory molecules were analysed in unconcentrated BALF samples from 10 sarcoidosis patients with CXR stage III and 10 patients with LS by semiquantitative protein array. Four novel molecules [CC chemokine ligand (CCL)15, CCL16, macrophage migration inhibitory factor (MIF) and macrophage stimulating protein (MSP)], detected for the first time in association with sarcoidosis, were then quantified by enzyme-linked immunosorbent assay in a second cohort of 68 sarcoidosis patients and 17 control subjects. The protein levels of CCL15, CCL16, CCL24, CXCL8, CXCL9, CXCL10, interleukin-16, MIF, MSP and matrix metallopeptidase 1 were increased in CXR stage III patients when compared with patients with LS. CCL15 and MSP up-regulation in CXR stage III patients in comparison with LS patients and controls was confirmed by enzyme-linked immunosorbent assay. Moreover, MSP was associated with treatment requirement (P = 0.001) and CCL15 was elevated in patients with disease progression at 2-year follow-up (P = 0.016). CCL16 levels were increased in sarcoidosis versus controls (P < 0.05), but no difference was observed between patient subgroups. MIF up-regulation was not confirmed in a larger patient group. In conclusion, chemokines CCL15, CCL16 and MSP were found elevated for the first time in BALF from sarcoidosis patients; our results showed that CCL15 and MSP may affect disease course.

• MeSH
• analýza rozptylu MeSH
• biologické markery analýza   MeSH
• bronchoalveolární lavážní tekutina chemie   MeSH
• chemokiny CC analýza   MeSH
• dospělí MeSH
• ELISA MeSH
• hepatocytární růstový faktor analýza   MeSH
• imunohistochemie MeSH
• inhibiční faktory migrace makrofágů analýza   MeSH
• intramolekulární oxidoreduktasy analýza   MeSH
• lidé středního věku MeSH
• lidé MeSH
• makrofágové zánětlivé proteiny analýza   MeSH
• matrixové metaloproteinasy analýza   MeSH
• mladý dospělý MeSH
• plicní sarkoidóza imunologie   MeSH
• progrese nemoci MeSH
• protoonkogenní proteiny analýza   MeSH
• studie případů a kontrol MeSH
• upregulace * MeSH
• zánět MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• srovnávací studie MeSH
• Názvy látek
• biologické markery MeSH
• CCL15 protein, human MeSH Prohlížeč
• CCL16 protein, human MeSH Prohlížeč
• chemokiny CC MeSH
• hepatocytární růstový faktor MeSH
• inhibiční faktory migrace makrofágů MeSH
• intramolekulární oxidoreduktasy MeSH
• macrophage stimulating protein MeSH Prohlížeč
• makrofágové zánětlivé proteiny MeSH
• matrixové metaloproteinasy MeSH
• MIF protein, human MeSH Prohlížeč
• protoonkogenní proteiny MeSH

BACKGROUND: CC chemokine ligand (CCL)5 and its receptor CCR5 contribute to leukocyte migration into lungs of patients with diffuse lung diseases (DLD). Pharmacological regulation of CCL5 and CCR5 expression was therefore explored in bronchoalveolar cells obtained from patients with DLD. METHODS: Cells from 21 patients were co-cultivated in vitro with tumour necrosis factor-alpha and dexamethasone, cyclosporin A (CyA) or pentoxifylline. Chemokine mRNA expression and protein production was assessed by reverse transcription-polymerase chain reaction and enzyme-linked immunosorbent assay, respectively. RESULTS: Dexamethasone altered CCL5 mRNA expression and suppressed its protein levels. CyA inhibited chemokine mRNA expression but not protein production. Pentoxifylline did not affected chemokine expression. Both dexamethasone and CyA suppressed CCR5 mRNA transcripts. CONCLUSION: In conclusion, while dexamethasone downregulates the CCL5 functional form, CyA and pentoxifylline have no effects on CCL5 protein. These data provide in vitro correlation for clinical applications of immunomodulators in therapy of DLD.

• MeSH
• bronchoalveolární lavážní tekutina cytologie   MeSH
• chemokin CCL5 MeSH
• chemokiny CC genetika   metabolismus   MeSH
• cyklosporin farmakologie   MeSH
• dexamethason farmakologie   MeSH
• dospělí MeSH
• glukokortikoidy farmakologie   MeSH
• imunosupresiva farmakologie   MeSH
• inhibitory enzymů farmakologie   MeSH
• kultivované buňky MeSH
• leukocyty cytologie   účinky léků   imunologie   metabolismus   MeSH
• lidé středního věku MeSH
• lidé MeSH
• messenger RNA metabolismus   MeSH
• pentoxifylin farmakologie   MeSH
• plicní nemoci metabolismus   patologie   MeSH
• receptory CCR5 genetika   metabolismus   MeSH
• senioři MeSH
• TNF-alfa 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
• CCL5 protein, human MeSH Prohlížeč
• chemokin CCL5 MeSH
• chemokiny CC MeSH
• cyklosporin MeSH
• dexamethason MeSH
• glukokortikoidy MeSH
• imunosupresiva MeSH
• inhibitory enzymů MeSH
• messenger RNA MeSH
• pentoxifylin MeSH
• receptory CCR5 MeSH
• TNF-alfa MeSH