BACKGROUND AND OBJECTIVE: MicroRNA (miRNA) are transcriptional regulators implicated in pulmonary sarcoidosis and packaged in extracellular vesicles (EV) during cellular communication. We characterized EV and investigated miRNA expression in bronchoalveolar lavage (BAL) fluid from sarcoidosis patients. METHODS: EV were characterized for size(s) using dynamic light scattering and transmission electron microscopy (TEM) analysis and protein markers by immunoblotting. Twelve extracellular and 5 cellular miRNA were investigated in BAL from 16 chest X-ray stage-I (CXR-I) and 17 CXR stage-II (CXR-II) sarcoidosis patients. Associations between miRNA and disease characteristics (extrapulmonary involvement, pulmonary function and BAL cell profile) were statistically analysed. RESULTS: BAL from sarcoidosis patients contained exosomes and microvesicles (MV) as EV. In these EV, expression of miR-146a (P = 0.007), miR-150 (P = 0.003) and BAL cellular miR-21 (P = 0.01) was increased in CXR-II compared with CXR-I. Other detected EV (miR-21 and miR-26a) and cellular (miR-31, miR-129-3p, miR-146a and miR-452) miRNA were not differentially expressed. The investigated miRNA did not reflect extrapulmonary involvement, but EV miR-146a and miR-150 were negatively correlated with pulmonary function (miR-146a with vital capacity (VC; Spearman's correlation coefficient (rs ), P = -0.657, 0.007), percent predicted forced expiratory volume in 1 s (FEV1 ; -0.662, 0.006) and FEV1 /forced vital capacity (FVC) ratio (-0.649, 0.008); miR-150 correlated negatively with VC (-0.584, 0.019) and FEV1 /FVC ratio (-0.746, 0.001) in CXR-II cases). CONCLUSION: Our data provide evidence that exosomes and microvesicles as extracellular vesicles are present in the bronchoalveolar space of sarcoidosis patients and they differentially express EV miRNA (miR-146a and miR-150), the expression of which correlates negatively with pulmonary function indices. The significance of these findings for disease pathophysiology and clinical course require further investigation.

• Klíčová slova
• bronchoalveolar lavage, exosomes, microRNA, microvesicles, pulmonary sarcoidosis,
• MeSH
• bronchoalveolární lavážní tekutina * MeSH
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mikro RNA genetika   MeSH
• plíce patofyziologie   MeSH
• plicní sarkoidóza * diagnóza   genetika   MeSH
• regulace genové exprese MeSH
• respirační funkční testy metody   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
• Názvy látek
• mikro RNA MeSH
• MIRN146 microRNA, human MeSH Prohlížeč
• MIRN150 microRNA, human MeSH Prohlížeč

BACKGROUND: For accuracy of quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR), normalisation with suitable reference genes is required. To date, no reference genes have been validated for expression studies of bronchoalveolar (BAL) cells. The aims of this study were to identify gene(s) with stable mRNA expression in BAL cells irrespective of gender, smoking, BAL cellular composition, lung pathology, treatment; and to assess the influence of reference genes on target gene expression data. RESULTS: The mRNA expression of ten housekeeping genes (ACTB, ARF1, CANX, G6PD, GAPDH, GPS1, GNB2L1, PSMB2, PSMD2, RPL32) was investigated by qRT-PCR in BAL cells from 71 subjects across a spectrum of lung diseases. The analyses were validated in an independent BAL cohort from 63 sarcoidosis patients and 17 control subjects. A second derivative method was used to calculate expression values (CTt); an equivalence test, applets BestKeeper, geNorm and NormFinder were applied to investigate gene expression stability. Of the investigated genes, PSMB2 (CTt +/- SD, 23.66 +/- 0.86) and RPL32 (18.65 +/- 0.92) were the most stable; both were constantly expressed in BAL samples from parallel investigated cohorts irrespective of evaluated variables. Finally, to demonstrate effect of traditional (ACTB/GAPDH) and novel (PSMB2/RPL32) reference genes as denominators, expression of two cytokines known associated with sarcoidosis was investigated in sarcoid BAL cells. While normalization with PSMB2/RPL32 resulted in elevated IFNG mRNA expression (p = 0.004); no change was observed using GAPDH/ACTB (p > 0.05). CCL2 mRNA up-regulation was observed only when PSMB2/RPL32 were used as denominators (p < 0.03). CONCLUSION: PSMB2 and RPL32 are, therefore, suitable reference genes to normalize qRT-PCR in BAL cells in sarcoidosis, and other interstitial lung disease.

• MeSH
• bronchy cytologie   MeSH
• dospělí MeSH
• kouření genetika   MeSH
• lidé středního věku MeSH
• lidé MeSH
• messenger RNA analýza   MeSH
• mladiství MeSH
• plicní alveoly cytologie   MeSH
• plicní nemoci genetika   MeSH
• polymerázová řetězová reakce s reverzní transkripcí normy   MeSH
• referenční standardy MeSH
• sarkoidóza genetika   MeSH
• stanovení celkové genové exprese normy   MeSH
• studie případů a kontrol MeSH
• zvířata MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• hodnotící studie MeSH
• práce podpořená grantem MeSH
• Názvy látek
• messenger RNA MeSH

BACKGROUND AND AIM: The chemokine Monocyte Chemoattractant Protein (MCP)-1/CCL2, a chemoattractant for mononuclear cells, has already been implicated in the pathogenesis of sarcoidosis. A single nucleotide polymorphism (SNP) located at the position -2518 (A to G) of the MCP-1 gene has been reported to alter production of the MCP-1 protein in vitro and ex vivo. The present study, therefore, explored a possible association between MCP-1-2518 SNP and pulmonary sarcoidosis including its clinical subtypes, especially Löfgren's syndrome (LS). Relationship between MCP-1-2518 SNP and serum MCP-1 levels was also investigated. METHODS: MCP-1-2518 genotypes were determined using PCR with sequence specific primers in 105 sarcoidosis patients and 359 healthy control subjects. The differences in genotype and allelic frequencies between the patient and control groups were assessed by chi2 test. MCP-1 protein concentrations in serum samples from 77 sarcoidosis patients were determined by ELISA; Mann-Whitney U-test was used to test for differences in protein levels. RESULTS: While there was no significant difference in distribution of MCP-1-2518 alleles between sarcoidosis patients and healthy control subjects, a significantly higher proportion of the MCP-1-2518*G allele (p = 0.01, odds ratio (OR) = 2.3) and of the GG genotype (p = 0.03, OR = 3.9) was observed in the patients with LS compared to control subjects. There was also a significantly higher frequency of the MCP-1-2518*G allele in patients presenting with LS compared to the patients without LS (p = 0.04, OR = 2.1). MCP-1 protein in serum was not related to MCP-1-2518 gene variants. CONCLUSION: A possible interpretation of our results is, that the MCP-1-2518 SNP or a gene located nearby may modify clinical manifestation of sarcoidosis towards Löfgren's syndrome. Future investigations in other population(s) should, therefore, follow this case-control study.

• MeSH
• alely MeSH
• chemokin CCL2 krev   genetika   MeSH
• dospělí MeSH
• genetická predispozice k nemoci MeSH
• genotyp MeSH
• jednonukleotidový polymorfismus * MeSH
• lidé středního věku MeSH
• lidé MeSH
• plicní sarkoidóza genetika   metabolismus   MeSH
• studie případů a kontrol MeSH
• syndrom 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
• Geografické názvy
• Česká republika MeSH
• Názvy látek
• chemokin CCL2 MeSH

BACKGROUND: Pulmonary sarcoidosis is a multisystem granulomatous disease with various clinical phenotypes. So far, there has been little information on protein patterns (PPs) of bronchoalveolar lavage fluid (BALF) from patients with sarcoidosis and no data are available on PPs in clinical disease subtypes. OBJECTIVES: To investigate the PP of BALF from patients with pulmonary sarcoidosis, to evaluate whether PPs reflect disease course as assessed by chest X-ray (CXR), and to compare PPs between patients with/without Löfgren's syndrome. METHODS: Surface-enhanced laser desorption/ionization-time-of-flight mass spectroscopy was applied to investigate PPs in unconcentrated BALF from 65 patients (CXR stage I, n = 32; CXR stage II, n = 22, CXR stage III, n = 11) and 23 healthy control subjects. The Mann-Whitney U test was used to detect differentially expressed protein peaks. After reversed-phase fractionation, peptide fingerprint mapping and immunodepletion were used to identify deregulated (up-regulated or down-regulated) proteins. RESULTS: Forty differentially expressed protein entities (2.75-185.62 kD) were detected in patients with pulmonary sarcoidosis versus control subjects (p < 0.05). Whereas 13 peaks (33%) were present across all CXR stages, 27 (67%) were specific for particular CXR stages. Comparison of PPs between CXR stage I patients with or without Löfgren's syndrome revealed 25 differentially expressed peaks. The total number of deregulated peaks and also of those associated with sarcoidosis as a whole were markedly lower in patients with Löfgren's syndrome in comparison with other sarcoid phenotypes. Human serum albumin, alpha1-antitrypsin, and protocadherin-2 precursor were identified from sarcoidosis-associated PP. CONCLUSION: Surface-enhanced laser desorption/ionization-time-of-flight mass spectroscopy enables determination of protein patterns in sarcoid BALF and allows detection of protein patterns linked to a particular disease course.

• MeSH
• alveolární makrofágy metabolismus   MeSH
• biologické markery analýza   MeSH
• bronchoalveolární lavážní tekutina chemie   cytologie   MeSH
• čipová analýza proteinů * MeSH
• dospělí MeSH
• down regulace MeSH
• lidé středního věku MeSH
• lidé MeSH
• neparametrická statistika MeSH
• peptidové mapování MeSH
• plicní sarkoidóza diagnóza   metabolismus   MeSH
• pravděpodobnost MeSH
• progrese nemoci MeSH
• proteiny genetika   metabolismus   MeSH
• referenční hodnoty MeSH
• respirační funkční testy MeSH
• senioři MeSH
• senzitivita a specificita MeSH
• spektrometrie hmotnostní - ionizace laserem za účasti matrice MeSH
• studie případů a kontrol MeSH
• stupeň závažnosti nemoci MeSH
• upregulace 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
• srovnávací studie MeSH
• Názvy látek
• biologické markery MeSH
• 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

In this study, messenger RNA (mRNA) expression for novel T lymphocyte chemoattractants, leukotactin-1, macrophage inflammatory protein (MIP)-3 alpha and MIP-3 beta was investigated in bronchoalveolar lavage fluid (BALF) cells from patients with sarcoidosis, a T cell-mediated disease with typical CD4+ lymphocyte alveolitis. Of these three chemokines, only MIP-3 beta mRNA was upregulated in sarcoidosis, and therefore, protein levels of this chemokine, its pharmacologic regulation, and association with disease clinical course were explored. MIP-3 beta protein concentrations were elevated in BALF from sarcoid patients compared with control subjects (p = 0.001) and in patients with chest X-ray stage II chemokine protein levels were increased compared with stage I (p = 0.003). MIP-3 beta protein was associated predominantly with alveolar macrophages and correlated with BALF lymphocytes and T cell subsets. mRNA expression for the MIP-3 beta receptor, CC chemokine receptor 7, was increased in sarcoidosis and correlated with MIP-3 beta protein levels. MIP-3 beta mRNA and protein expression in BALF cells was suppressed by dexamethasone and cyclosporine A in vitro. In conclusion, MIP-3 beta is implicated in T lymphocyte recruitment in sarcoidosis, is associated with disease progression, and is downregulated by drugs used for sarcoidosis treatment. This novel chemokine, therefore, represents a candidate for studies of sarcoidosis pathobiologic mechanisms.

• MeSH
• aktivace lymfocytů účinky léků   imunologie   MeSH
• alveolární makrofágy účinky léků   imunologie   MeSH
• bronchoalveolární lavážní tekutina chemie   MeSH
• chemokin CCL19 MeSH
• chemokin CCL20 MeSH
• chemokiny CC analýza   genetika   imunologie   MeSH
• cyklosporin imunologie   terapeutické užití   MeSH
• dexamethason imunologie   terapeutické užití   MeSH
• dospělí MeSH
• down regulace účinky léků   MeSH
• exprese genu * účinky léků   genetika   imunologie   MeSH
• imunohistochemie MeSH
• lidé středního věku MeSH
• lidé MeSH
• makrofágové zánětlivé proteiny analýza   genetika   imunologie   MeSH
• messenger RNA analýza   MeSH
• plicní sarkoidóza krev   farmakoterapie   imunologie   patologie   MeSH
• polymerázová řetězová reakce s reverzní transkripcí MeSH
• progrese nemoci MeSH
• receptory CCR6 MeSH
• receptory chemokinů * MeSH
• senioři MeSH
• studie případů a kontrol MeSH
• stupeň závažnosti nemoci MeSH
• T-lymfocyty účinky léků   imunologie   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
• CCL19 protein, human MeSH Prohlížeč
• CCL20 protein, human MeSH Prohlížeč
• CCR6 protein, human MeSH Prohlížeč
• chemokin CCL19 MeSH
• chemokin CCL20 MeSH
• chemokiny CC MeSH
• cyklosporin MeSH
• dexamethason MeSH
• makrofágové zánětlivé proteiny MeSH
• messenger RNA MeSH
• receptory CCR6 MeSH
• receptory chemokinů * MeSH

BACKGROUND: Chemotactic cytokines (chemokines) have been recently implicated in the pathogenesis of interstitial lung diseases. A novel chemokine called pulmonary and activation-regulated chemokine (PARC/CCL18), which attracts lymphocytes in vitro, has been detected in the human lung. We have, therefore, investigated PARC mRNA expression in bronchoalveolar lavage fluid (BALF) cells of patients with pulmonary sarcoidosis-a disease characterised by a lymphocytic infiltrate. Further, because several immunomodulators are used in the treatment of sarcoidosis, we have determined the effects of selected drugs on PARC mRNA expression in vitro. SUBJECTS AND METHODS: BALF cells were obtained by standard bronchoalveolar lavage (BAL) from 30 patients with pulmonary sarcoidosis (S) and 16 control subjects (C). BALF cells from seven subjects were cultured in the presence of dexamethasone (Dx), cyclosporin A (CyA) and pentoxifylline (Px). PARC mRNA expression was semiquantitated by reverse-transcription polymerase chain reaction (RT-PCR) using normalisation to the expression of the beta-actin gene. RESULTS: PARC mRNA transcripts were detected in 87% of all investigated BALF samples. The expression (ODR PARC/beta-actin; median, the first to the third quartile range) was similar in both groups tested (S, 0.60 (0.50-0.95); C, 0.59 (0.36-0.93); S vs. C: P>0.05). PARC mRNA expression was not associated with the number of lymphocytes in bronchoalveolar space. PARC mRNA expression was significantly suppressed by Dx (P=0.02); CyA and Px showed a moderate inhibitory effect which did not attain significance. CONCLUSION: mRNA for the chemokine PARC is expressed in the lower respiratory tract in both healthy subjects and patients with pulmonary sarcoidosis. Out of the three immunomodulatory drugs tested, Dx downregulates PARC mRNA expression in BALF cells in vitro.

• MeSH
• adjuvancia imunologická farmakologie   MeSH
• bronchoalveolární lavážní tekutina cytologie   imunologie   MeSH
• chemokiny CC genetika   MeSH
• cyklosporin farmakologie   MeSH
• dexamethason farmakologie   MeSH
• DNA genetika   MeSH
• dospělí MeSH
• exprese genu účinky léků   MeSH
• imunosupresiva farmakologie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• messenger RNA genetika   metabolismus   MeSH
• pentoxifylin farmakologie   MeSH
• plicní sarkoidóza farmakoterapie   genetika   imunologie   patologie   MeSH
• počet buněk MeSH
• sekvence nukleotidů MeSH
• senioři MeSH
• techniky in vitro 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
• adjuvancia imunologická MeSH
• CCL18 protein, human MeSH Prohlížeč
• chemokiny CC MeSH
• cyklosporin MeSH
• dexamethason MeSH
• DNA MeSH
• imunosupresiva MeSH
• messenger RNA MeSH
• pentoxifylin MeSH

The CC chemokine receptor 5 (CCR5) binds the chemokine ligands RANTES (CCL5) and MIP-1alpha (CCL3), which have been implicated in the development of alveolitis in sarcoidosis. We have, therefore, investigated CCR5 mRNA expression in bronchoalveolar lavage fluid (BALF) cells from patients with sarcoidosis. Further, we explored whether there was any association between CCR5 mRNA expression and the presence of the CCR5Delta32 DNA polymorphism. Semiquantitative RT-PCR was used to determine CCR5 mRNA expression from BALF cells from 16 control subjects (C) and 39 patients with sarcoidosis (S). The data on the CCR5Delta32 polymorphism, determined by PCR-SSP, were available for 37 patients. CCR5 mRNA expression was significantly upregulated in sarcoidosis (median+/-SEM, C, 0.00+/-0.07; S, 0.12+/-0.07; P<0.05). When patients were evaluated according to their CCR5Delta32 genotype, an interesting trend emerged with Delta32 positive patients (wt, mt) expressing less mRNA than the patients with both wild-type alleles (wt, wt): 0.00+/-0.09, and 0.26+/-0.09, respectively; P>0.05). In conclusion, upregulation of CCR5 mRNA in BALF of patients with sarcoidosis is consistent with its chemokine ligands RANTES and MIP-1alpha playing a pivotal role in inflammatory cell recruitment to disease sites. Though the data from this pilot study had no clinical correlations we suggest that further studies are warranted on the role of this Th1 subset marker in the pathogenesis of sarcoidosis.

• MeSH
• bronchoalveolární lavážní tekutina cytologie   MeSH
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• messenger RNA genetika   metabolismus   MeSH
• plicní sarkoidóza genetika   MeSH
• polymerázová řetězová reakce s reverzní transkripcí MeSH
• polymorfismus genetický genetika   MeSH
• receptory CCR5 genetika   MeSH
• regulace genové exprese * 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
• Názvy látek
• messenger RNA MeSH
• receptory CCR5 MeSH

Members of the interleukin-1 (IL-1) family are implicated in the pathogenesis of sarcoidosis and idiopathic pulmonary fibrosis (IPF). We have, therefore, performed a case-control study to investigate a plausible association between sarcoidosis and the polymorphisms in the IL-1alpha, IL-1beta, and IL-1 receptor antagonist (IL-1Ra) genes. Further, as a separate question, we explored whether the aforementioned genes of the IL-1 cluster are associated with IPF. Using PCR with sequence-specific primers, IL-1alpha -889, IL-1beta -511, IL-1beta +3953, and IL-1Ra intron 2 VNTR polymorphisms were determined in 348 white subjects of West Slavonic ancestry (95 patients with sarcoidosis, 54 patients with IPF, and 199 healthy control subjects). The IL-1alpha -889 1.1 genotype was significantly overrepresented in patients with sarcoidosis in comparison with control subjects (60.0 versus 44.2%, p = 0.012, p(corr) = 0.047). The distribution of IL-1beta -511, IL-1beta +3953, and IL-1Ra VNTR genotypes and alleles did not significantly differ between the cases and controls. No association between IPF and the investigated polymorphisms was found. Strong linkage disequilibrium between pairs of polymorphic loci was observed. Further population studies are warranted to confirm the observed association between sarcoidosis and the IL-1alpha polymorphism and also to explore mechanisms of IL-1alpha -889 participation in aberrant immune response in sarcoidosis.

• MeSH
• dospělí MeSH
• exprese genu genetika   MeSH
• frekvence genu genetika   MeSH
• interleukin-1 genetika   MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• multigenová rodina genetika   MeSH
• plicní fibróza genetika   MeSH
• plicní sarkoidóza genetika   MeSH
• polymerázová řetězová reakce MeSH
• polymorfismus genetický genetika   MeSH
• receptory interleukinu-1 antagonisté a inhibitory   genetika   MeSH
• senioři MeSH
• studie případů a kontrol MeSH
• vazebná nerovnováha genetika   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• interleukin-1 MeSH
• receptory interleukinu-1 MeSH