The MCP-1/CCL2 as well as RANTES/CCL5 chemokines are potent chemoattractants involved in immunoregulatory and inflammatory processes of rheumatoid arthritis. Recent studies demonstrated elevated levels of MCP-1 and RANTES in plasma, synovial fluid, and the synovial tissue of patients with RA. To examine the relationship among MCP-1 and RANTES single nucleotide polymorphisms and circulating levels and rheumatoid arthritis (RA), a total of 156 RA patients and 125 controls were recruited into the study. An association of -855 C/G MCP-1 polymorphism to IgM RF within the RA patients was observed. The lowest circulating levels of RANTES were observed in the AA variant of RANTES -403 G/A polymorphism. Furthermore, an association of -403 AA variant to circulating levels of IL-15 and IL-10 was found. No associations of factors describing rheumatoid arthritis (RFs, ANA, anti-CCP-positive/negative, DAS 28 score and number of swollen joints) with MCP-1 levels, genotype distribution, allelic frequencies and/or frequencies of haplotypes composed of all three studied polymorphisms in promoter region of MCP-1, and RANTES polymorphism were observed. We conclude that the RANTES promoter polymorphism is associated to circulating levels of RANTES, IL15 and IL10. However, our findings suggest that polymorphisms in the MCP-1 and RANTES gene promoters do not contribute significantly to the interindividual RA susceptibility and/or severity in Caucasians.

• MeSH
• chemokin CCL2 krev   genetika   imunologie   MeSH
• chemokin CCL5 krev   genetika   imunologie   MeSH
• dospělí MeSH
• imunoglobulin M genetika   imunologie   MeSH
• interleukin-10 krev   MeSH
• interleukin-15 krev   MeSH
• jednonukleotidový polymorfismus MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladý dospělý MeSH
• promotorové oblasti (genetika) MeSH
• revmatoidní artritida genetika   imunologie   MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• synoviální membrána metabolismus   MeSH
• synoviální tekutina metabolismus   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• CCL2 protein, human MeSH Prohlížeč
• CCL5 protein, human MeSH Prohlížeč
• chemokin CCL2 MeSH
• chemokin CCL5 MeSH
• imunoglobulin M MeSH
• interleukin-10 MeSH
• interleukin-15 MeSH

Coronary artery inflammation is a critical process in the pathogenesis of myocardial infarction (MI). The chemokine CCL5/RANTES (regulated upon activation, normal T cells expressed and secreted) is expressed in advanced atherosclerotic lesions. Functional polymorphisms of the RANTES gene can, therefore, be involved in the pathogenesis of coronary artery disease. We examined the association of polymorphisms in the RANTES gene with myocardial infarction in Slavonic populations of Czech and Russian origin. A total of 467 post-MI patients and 337 control subjects were genotyped for RANTES promoter G-403A (rs2107538) and intron 1.1 T/C (rs2280789) variants by PCR-SSP. Both RANTES genotypes and allele frequencies did not differ between case and control groups. Haplotype-based analysis also failed to reveal an association between MI and investigated markers. Strong linkage disequilibrium was detected between particular RANTES alleles. The data do not support an association between RANTES G-403A polymorphism and MI, as reported previously.

• MeSH
• běloši genetika   MeSH
• chemokin CCL5 genetika   imunologie   MeSH
• dospělí MeSH
• genetická predispozice k nemoci MeSH
• genotyp MeSH
• infarkt myokardu genetika   imunologie   MeSH
• jednonukleotidový polymorfismus * MeSH
• lidé středního věku MeSH
• lidé MeSH
• nemoci koronárních tepen genetika   MeSH
• promotorové oblasti (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
• Geografické názvy
• Česká republika MeSH
• Rusko MeSH
• Názvy látek
• chemokin CCL5 MeSH

The chemokine "regulated on activation, normal T-cell expressed and secreted" (RANTES) is a potent eosinophil and lymphocyte attractant with particular preference for CD45RO+ T-cells and eosinophils. These cells accumulate in the lungs of patients with sarcoidosis and fibrosing alveolitis. The purpose of this study was to determine whether RANTES mediates the inflammatory cell influx in these diffuse lung diseases. Cell types and number of bronchoalveolar cells expressing RANTES protein were investigated by immunocytochemistry using lavage cells obtained from 22 patients and 11 control subjects. Subsequently, RANTES messenger ribonucleic acid (mRNA) was semiquantitated using reverse transcription polymerase chain reaction (RT-PCR) methodology in unseparated lavage cell pellets in 26 patients and 13 control subjects. Cells expressing RANTES mRNA were identified by in situ hybridization. RANTES protein expression in lower respiratory tract (LRT) cells was identified in all study groups. The percentage of RANTES+ lavage cells in sarcoidosis was higher than in controls. RANTES was localized in the cytoplasm, mainly in alveolar macrophages (CD68+ cells) in sarcoidosis, and both in alveolar macrophages and eosinophils in fibrosing alveolitis. The same cell types which expressed RANTES protein expressed RANTES mRNA, as assessed by in situ hybridization. Sarcoidosis patients had higher levels of RANTES mRNA than the other groups. RANTES protein was higher in individuals with abnormal lymphocyte numbers: RANTES protein and mRNA expression was significantly correlated with lavage CD45RO+ lymphocyte numbers. These results indicate that RANTES may mediate T-lymphocyte influx in diffuse lung disease, particularly sarcoidosis. Moreover, they suggest that the cellular source of RANTES is the alveolar macrophage in sarcoidosis, and both macrophages and eosinophils in fibrosing alveolitis.

• MeSH
• alveolární makrofágy metabolismus   MeSH
• antigeny CD45 analýza   MeSH
• bronchoalveolární lavážní tekutina cytologie   MeSH
• chemokin CCL5 genetika   metabolismus   MeSH
• eozinofily metabolismus   MeSH
• hybridizace in situ MeSH
• imunohistochemie MeSH
• intersticiální plicní nemoci metabolismus   MeSH
• lidé středního věku MeSH
• lidé MeSH
• lymfocyty imunologie   metabolismus   MeSH
• messenger RNA metabolismus   MeSH
• neutrofily metabolismus   MeSH
• plicní fibróza metabolismus   MeSH
• plicní sarkoidóza metabolismus   MeSH
• počet lymfocytů MeSH
• polymerázová řetězová reakce MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• antigeny CD45 MeSH
• chemokin CCL5 MeSH
• messenger RNA MeSH

Tick-borne encephalitis virus (TBEV) targets the central nervous system (CNS), leading to potentially severe neurological complications. The neurovascular unit plays a fundamental role in the CNS and in the neuroinvasion of TBEV. However, the role of human brain pericytes, a key component of the neurovascular unit, during TBEV infection has not yet been elucidated. In this study, TBEV infection of the primary human brain perivascular pericytes was investigated with highly virulent Hypr strain and mildly virulent Neudoerfl strain. We used Luminex assay to measure cytokines/chemokines and growth factors. Both viral strains showed comparable replication kinetics, peaking at 3 days post infection (dpi). Intracellular viral RNA copies peaked at 6 dpi for Hypr and 3 dpi for Neudoerfl cultures. According to immunofluorescence staining, only small proportion of pericytes were infected (3% for Hypr and 2% for Neudoerfl), and no cytopathic effect was observed in the infected cells. In cell culture supernatants, IL-6 production was detected at 3 dpi, together with slight increases in IL-15 and IL-4, but IP-10, RANTES and MCP-1 were the main chemokines released after TBEV infection. These chemokines play key roles in both immune defense and immunopathology during TBE. This study suggests that pericytes are an important source of these signaling molecules during TBEV infection in the brain.

• Klíčová slova
• CCL5, CXCL10, chemokine, flavivirus, human pericytes, infection, inflammation, tick-borne encephalitis virus,
• MeSH
• chemokin CCL5 * metabolismus   MeSH
• chemokin CXCL10 * metabolismus   MeSH
• cytokiny metabolismus   MeSH
• klíšťová encefalitida * virologie   metabolismus   MeSH
• kultivované buňky MeSH
• lidé MeSH
• mozek * virologie   metabolismus   patologie   MeSH
• pericyty * virologie   metabolismus   MeSH
• replikace viru MeSH
• viry klíšťové encefalitidy * fyziologie   patogenita   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• CCL5 protein, human MeSH Prohlížeč
• chemokin CCL5 * MeSH
• chemokin CXCL10 * MeSH
• CXCL10 protein, human MeSH Prohlížeč
• cytokiny MeSH

Chemokines, including RANTES, play a crucial role in the processes of inflammation during cardiovascular disorders, including myocardial infarction, disease progression and complications. This study aimed to evaluate the role of RANTES -403G/A polymorphism and levels in circulation in processes of development and progression of myocardial infarction and cardiogenic shock. A total of 609 patients with ST-segment elevation myocardial infarction, 43 patients with cardiogenic shock and 130 control subjects were enrolled in the study. RANTES -403G/A promoter polymorphism and baseline serum RANTES levels were analyzed. In the present study, we associated RANTES -403G/A promoter polymorphism with acute heart failure in patients with myocardial infarction (p = 0.006) and ejection fraction 3 months after MI onset (p = 0.02). Further, a difference in circulating RANTES levels among controls and STEMI subjects, and a relation of serum levels with acute heart failure was observed (p = 0.03, p = 0.003, respectively). We found a significant difference when comparing cardiogenic shock patients and controls (p < 0.001), with the most significant difference between cardiogenic shock and AHF subgroup of STEMI patients (p < 0.001). We observed a decreasing tendency of serum RANTES levels with the severity of myocardial infarction and progression, with the lowest levels in patients with cardiogenic shock (cutoff level ≥80.4 ng/ml). Our results suggest the role of RANTES as a potential biomarker of cardiogenic shock and acute heart failure in the hospital phase after myocardial infarction.

• MeSH
• analýza přežití MeSH
• biologické markery krev   MeSH
• chemokin CCL5 krev   genetika   MeSH
• dospělí MeSH
• infarkt myokardu krev   genetika   MeSH
• jednonukleotidový polymorfismus * MeSH
• kardiogenní šok krev   genetika   patologie   MeSH
• kohortové studie MeSH
• lidé středního věku MeSH
• lidé MeSH
• progrese nemoci MeSH
• promotorové oblasti (genetika) * MeSH
• senioři MeSH
• srdeční selhání genetika   patologie   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
• biologické markery MeSH
• chemokin CCL5 MeSH

Alzheimer's disease (AD) is the most common type of dementia, but it is very difficult to diagnose with certainty, so many AD studies have attempted to find early and relevant diagnostic markers. Regulated upon activation, normal T cell expressed and secreted (RANTES, also known as C-C chemokine ligand) is a chemokine involved in the migration of T cells and other lymphoid cells. Changes in RANTES levels and its expression in blood or in cerebrospinal fluid have been reported in some neurodegenerative diseases, such as Parkinson's disease and multiple sclerosis, but also in metabolic diseases in which inflammation plays a role. The aim of this observational study was to assess RANTES levels in peripheral blood as clinical indicators of AD. Plasma levels of RANTES were investigated in 85 AD patients in a relatively early phase of AD (median 8.5 months after diagnosis; 39 men and 46 women; average age 75.7 years), and in 78 control subjects (24 men and 54 women; average age 66 years). We found much higher plasma levels of RANTES in AD patients compared to controls. A negative correlation of RANTES levels with age, disease duration, Fazekas scale score, and the medial temporal lobe atrophy (MTA) score (Scheltens's scale) was found in AD patients, i.e., the higher levels corresponded to earlier stages of the disease. Plasma RANTES levels were not correlated with cognitive scores. In AD patients, RANTES levels were positively correlated with the levels of pro-inflammatory cytokines interleukin-6 and tumor necrosis factor-α, which is consistent with the well-known fact that AD is associated with inflammatory processes. RANTES levels were also positively correlated with insulin levels in AD patients, with insulin resistance (HOMA-R) and pancreatic beta cell function (HOMA-F). This study evaluated several clinical and metabolic factors that may affect plasma levels of RANTES, but these factors could not explain the increases in RANTES levels observed in AD patients. Plasma levels of RANTES appear to be an interesting peripheral marker for early stages of AD. The study was approved by the Ethics Committee of Institute of Endocrinology, Prague, Czech Republic on July 22, 2011.

• Klíčová slova
• Alzheimer’s disease, RANTES, biomarker, central nervous system, cognitive impairment, inflammation,
• Publikační typ
• časopisecké články MeSH

Development of a novel group of antiviral agents, acyclic nucleoside phosphonates, has provided a new perspective for treating human immunodeficiency virus (HIV) infection. One of the compounds, 9-(R)-[2-(phosphonomethoxy)propyl]adenine (PMPA) (tenofovir), has been shown to confer complete protection against AIDS in a simian model of the infection. The aim of our study was to investigate whether the antiviral efficacy of PMPA, which depends mainly on inhibition of virus-induced DNA polymerase or of reverse transcriptase, could be contributed by immunomodulatory potential of this drug. We screened for its ability to activate production of cytokines and chemokines that are known to interfere with the replication and/or the entry of HIV in cells. Using the in vitro test system of mouse macrophages and lymphocytes, it has been found that PMPA stimulates macrophage secretion of interleukin-1beta (IL-1beta), IL-10, and tumor necrosis factor alpha. Production of the chemokines RANTES and macrophage inflammatory protein 1alpha was activated in both macrophages and lymphocytes, and also in human cell line U937. Other cytokines--i.e., IL-2, IL-12, IL-13, and gamma interferon-remained uninfluenced by PMPA. The cytokines were stimulated in a dose-dependent fashion, with rapid onset, and peak concentrations were achieved within 5 to 24 h. The findings contribute to a more complex understanding of mechanisms of antiviral effectiveness of PMPA and support the view that this drug could become a promising candidate for therapeutic exploitation in anti-HIV preventive medicine.

• MeSH
• adenin analogy a deriváty   farmakologie   MeSH
• chemokin CCL4 MeSH
• chemokin CCL5 metabolismus   MeSH
• chemokiny fyziologie   MeSH
• cytokiny fyziologie   MeSH
• interleukin-1 metabolismus   MeSH
• interleukin-10 metabolismus   MeSH
• kultivované buňky MeSH
• látky proti HIV farmakologie   MeSH
• makrofágové zánětlivé proteiny metabolismus   MeSH
• makrofágy účinky léků   metabolismus   MeSH
• myši inbrední C57BL MeSH
• myši MeSH
• organofosfonáty * MeSH
• organofosforové sloučeniny farmakologie   MeSH
• tenofovir MeSH
• TNF-alfa metabolismus   MeSH
• zvířata MeSH
• Check Tag
• myši MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• adenin MeSH
• chemokin CCL4 MeSH
• chemokin CCL5 MeSH
• chemokiny MeSH
• cytokiny MeSH
• interleukin-1 MeSH
• interleukin-10 MeSH
• látky proti HIV MeSH
• makrofágové zánětlivé proteiny MeSH
• organofosfonáty * MeSH
• organofosforové sloučeniny MeSH
• tenofovir MeSH
• TNF-alfa MeSH

Antiarthritic effects of two acyclic nucleoside phosphonates, 9-(2-phosphonomethoxyethyl)adenine (PMEA; Adefovir) and 9-(2-phosphonomethoxypropyl)adenine (PMPA), as well as their more bioavailable prodrugs, bis(pivaloyloxymethyl)ester of PMEA [bis(POM)-PMEA; Adefovir Dipivoxil] and bis(isopropyloxycarbonyloxymethyl)ester of PMPA [bis(POC)-PMPA], were investigated in a model of adjuvant-induced arthritis in Lewis rats. The drugs were injected subcutaneously at doses of 5-50 mg/kg. PMEA and its prodrug inhibited by > 80% arthritic paw swelling, splenomegaly and fibroadhesive perisplenitis. Both prophylactic and therapeutic dosing regimens were effective. Neither PMPA nor bis(POC)-PMPA suppressed development of arthritic lesions. Substantially reduced nitrite + nitrate levels were detected in serum and urine of PMEA-treated animals as compared to those of untreated diseased controls. Also, complete suppression of the disease-associated, greatly enhanced systemic levels of the chemokine, RANTES (regulated upon activation, normal T cell expressed and secreted), was observed in rats injected with PMEA. Additional in vitro studies showed that PMEA does not change, PMPA enhances, and both prodrugs inhibit the immune-activated NO production. Under the same conditions PMEA inhibits, while PMPA slightly stimulates, secretion of RANTES. Collectively, these data suggest that the in vivo-inhibited production of nitric oxide (NO) is a consequence rather than a mechanism of antiarthritic action of PMEA. Possible mechanisms for the anti-RANTES activity of PMEA remains to be firmly established.

• MeSH
• adenin analogy a deriváty   farmakologie   MeSH
• antiflogistika nesteroidní farmakologie   MeSH
• artritida experimentální farmakoterapie   metabolismus   patologie   MeSH
• chemokin CCL5 biosyntéza   krev   MeSH
• fibróza MeSH
• krysa rodu Rattus MeSH
• organofosfonáty * MeSH
• organofosforové sloučeniny farmakologie   MeSH
• oxid dusnatý biosyntéza   krev   moč   MeSH
• peritoneální makrofágy účinky léků   metabolismus   MeSH
• potkani inbrední LEW MeSH
• prekurzory léčiv farmakologie   MeSH
• slezina patologie   MeSH
• tenofovir MeSH
• velikost orgánu účinky léků   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• srovnávací studie MeSH
• Názvy látek
• adefovir MeSH Prohlížeč
• adenin MeSH
• antiflogistika nesteroidní MeSH
• bis(isopropyloxymethylcarbonyl) 9-(2-phosphonomethoxypropyl)adenine MeSH Prohlížeč
• bis(pivaloyloxymethyl)-9-(2-phosphonylmethoxyethyl)adenine MeSH Prohlížeč
• chemokin CCL5 MeSH
• organofosfonáty * MeSH
• organofosforové sloučeniny MeSH
• oxid dusnatý MeSH
• prekurzory léčiv MeSH
• tenofovir MeSH

The chemokines RANTES (regulated on activation, T-cell expressed and secreted; CC chemokine ligand (CCL)-5) and monocyte inflammatory protein (MIP)-1alpha (CCL-3) have been implicated in the development of alveolitis in pulmonary sarcoidosis. The novel C chemokine single cysteine motif (SCM)-1alpha (XCL-1) and the CC chemokine monocyte chemoattractant protein (MCP)-1 (CCL-2) are also mononuclear-cell attractants and represent alternative candidate mediators of alveolitis. Therefore, the expression of MCP-1 and SCM-1alpha was investigated together with the expression of RANTES and MIP-1alpha in bronchoalveolar lavage fluid (BALF) from control subjects and patients with sarcoidosis. The relationship between chemokine expression and sarcoidosis clinical course was also explored. Messenger ribonucleic acid (mRNA) expression for all four chemokines was determined by semiquantitative reverse transcriptase-polymerase chain reaction of RNA extracted from unseparated bronchoalveolar cells (17 patients, 12 controls). RANTES, MIP-1alpha and MCP-1 proteins were measured by enzyme-linked immunosorbent assay of unconcentrated BALF (60 patients, 17 controls). MCP-1, and namely RANTES and SCM-1alpha mRNA expression was upregulated in sarcoidosis, particularly in patients with more advanced disease. RANTES, and namely MCP-1 concentrations were elevated in BALF samples obtained from patients; MCP-1 levels were most increased in patients with chest radiographic stage 2 disease and also in patients with persistent and recurrent disease. In conclusion, chemokines monocyte chemotactive protein-1 and single cysteine motif-1alpha are, in addition to RANTES, associated with the development of alveolitis in sarcoidosis and their expression parallels the disease course.

• MeSH
• bronchoalveolární lavážní tekutina chemie   cytologie   MeSH
• chemokin CCL2 genetika   metabolismus   MeSH
• chemokin CCL3 MeSH
• chemokin CCL4 MeSH
• chemokin CCL5 genetika   metabolismus   MeSH
• chemokiny C genetika   metabolismus   MeSH
• chemokiny CC genetika   metabolismus   MeSH
• dospělí MeSH
• ELISA MeSH
• exprese genu MeSH
• lidé MeSH
• makrofágové zánětlivé proteiny genetika   metabolismus   MeSH
• messenger RNA analýza   MeSH
• plicní sarkoidóza metabolismus   MeSH
• polymerázová řetězová reakce s reverzní transkripcí MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• chemokin CCL2 MeSH
• chemokin CCL3 MeSH
• chemokin CCL4 MeSH
• chemokin CCL5 MeSH
• chemokiny C MeSH
• chemokiny CC MeSH
• makrofágové zánětlivé proteiny MeSH
• messenger RNA MeSH
• XCL1 protein, human MeSH Prohlížeč

BACKGROUND: Chemokines and chemokine receptors are major mediators of leukocyte trafficking into the sites of the immune response. They participate in defence against microbial infection, in Th1/Th2 polarization of the immune response, allograft rejection and angiogenesis/angiostasis as well as in tumorigenesis and metastasis. To date, several functional polymorphisms of chemokine and chemokine receptor genes have been discovered that are able to deregulate chemokine system and, therefore, they may interfere with the pathogenesis of a large number of inflammatory and other diseases. In this review we focus on the known polymorphisms of two chemokines: CCL2, CCL5 and their corresponding receptors (CCR2, CCR5) and we also discuss their associations with susceptibility and progression to selected immune-mediated diseases. METHODS AND RESULTS: Based on relevant literature this article gives a short overview of case-control and family studies regarding effect of the genetic factors on diseases such as coronary artery disease, systemic lupus erythematosus, diabetes mellitus, lung diseases and others. CONCLUSION: Recent advance in the identification of chemokine genetic background of the diseases could provide opportunity for pharmacological treatment. However, we need more information about posttranscriptional events to understand functional relevance of polymorphisms and to discovery new avenues to blocking disease development.

• MeSH
• chemokin CCL2 genetika   MeSH
• chemokin CCL5 genetika   imunologie   fyziologie   MeSH
• lidé MeSH
• polymorfismus genetický * MeSH
• receptory CCR2 genetika   imunologie   fyziologie   MeSH
• receptory CCR5 genetika   imunologie   fyziologie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH
• Názvy látek
• chemokin CCL2 MeSH
• chemokin CCL5 MeSH
• receptory CCR2 MeSH
• receptory CCR5 MeSH