Chemokines Dotaz Zobrazit nápovědu
Chemokines are chemotactic cytokines produced by leukocytes and other types of cells including tumor cells. Their action is determined by the expression of cognate receptors and subsequent signaling in target cells, followed by the modulation of cytoskeletal proteins and the induction of other responses. In tumors, chemokines produced by neoplastic/stroma cells control the leukocyte infiltrate influencing tumor growth and progression. Tumor cells also express functional chemokine receptors responding to chemokine signals, promoting cell survival, proliferation and metastasis formation. Chemokines may be detected in serum of cancer patients, but due to the paracrine nature of these molecules, more significant concentrations are found in the tumor adjacent, non-vascular fluids, collectively called tumor proximal fluids. This review summarizes the expression of CC and CXC chemokines in these fluids, namely in interstitial fluid, pleural, ascitic, and cyst fluids, but also in urine, saliva, cerebrospinal fluid, cervical secretions and bronchoalveolar lavage fluid. Most comparative clinical studies reveal increased chemokine levels in high-grade tumor proximal fluids rather than in low-grade tumors and benign conditions, indicating shorter survival periods. The data confirm peritumoral fluid chemokines as sensitive diagnostic and prognostic markers, as well as offer support for chemokines and their receptors as potential targets for antitumor therapy.
- Klíčová slova
- chemokine, chemokine receptors, metastasis, tumor proximal fluids,
- MeSH
- ascitická tekutina chemie MeSH
- bronchoalveolární lavážní tekutina chemie MeSH
- cervikální hlen chemie MeSH
- chemokiny metabolismus MeSH
- extracelulární tekutina chemie MeSH
- lidé MeSH
- metastázy nádorů MeSH
- moč chemie MeSH
- mozkomíšní mok chemie MeSH
- nádory metabolismus MeSH
- pleura metabolismus MeSH
- receptory chemokinů metabolismus MeSH
- sliny chemie MeSH
- tělesné tekutiny chemie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
- Názvy látek
- chemokiny MeSH
- receptory chemokinů MeSH
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
Goeckerman's therapy (GT) of psoriasis is based on daily application of pharmacy grade coal tar on affected skin with subsequent exposure to UV light. The aim of this study was to evaluate the influence of Goeckerman's therapy of psoriasis on the levels of proangiogenic chemokines ENA-78 (CXCL5, Epithelial Cell Derived Neutrophil Attractant-78), GRO alpha (CXCL1, Growth-Related Oncogene), IL-8 (CXCL8, Interleukin-8), MCP-1 (CCL2, Monocyte Chemotactic (Chemoattractant) Protein 1) and RANTES (CCL5, Regulated on Activation of Normal T Cell Expressed and Secreted) in peripheral blood of 22 children's patients with psoriasis. 22 otherwise healthy children serve as a control group. The serum levels of chemokines were determined by commercial membrane protein array technique (RayBiotech, USA). Efficacy of Goeckerman's therapy was delineated by PASI score. Disease activity was significantly diminished by Goeckerman's therapy (p < 0.001). Serum levels of GRO alpha and MCP-1 in patients before GT were significantly higher than those measured in healthy blood donors (GRO alpha: p = 0.0128 and MCP-1: p = 0.0003). Serum levels of GRO alpha, MCP-1 and RANTES were significantly diminished by GT (GRO alpha: p = 0.002, MCP-1: p = 0.048 and RANTES: p = 0.0131). Compared to the healthy controls, serum level of MCP-1 remained significantly increased in psoriasis patients after GT (p < 0.0001). In conclusion, we found that the GT of psoriasis influenced the serum levels of proinflammatory and proangiogenic chemokines, especially GRO alpha, MCP-1 and RANTES. It could be the cause for decreased proangiogenic activity which is described after GT of psoriasis.
- MeSH
- chemokiny CC krev MeSH
- chemokiny CXC krev MeSH
- čipová analýza proteinů MeSH
- dehet uhelný aplikace a dávkování MeSH
- dítě MeSH
- keratolytika aplikace a dávkování MeSH
- lidé MeSH
- mladiství MeSH
- psoriáza krev terapie MeSH
- terapie ultrafialovými paprsky * MeSH
- Check Tag
- dítě MeSH
- lidé MeSH
- mladiství MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- chemokiny CC MeSH
- chemokiny CXC MeSH
- dehet uhelný MeSH
- keratolytika MeSH
Chemokines form a new superfamily of small glycoproteins. They are key molecules that activate and direct the migration of different types of leukocytes from the blood stream into sites of infection and inflammation. In addition to this role certain chemokines have been reported to act on different types of cells (e.g. hematopoietic progenitor cells, dendritic cells, fibroblasts, keratinocytes). Other of them also play a role in wound healing, in angiogenesis and in viral infections. These molecules have a high degree of amino acid sequence homology and they have four conserved cysteins forming two essential disulphide bonds. They are divided into four classes (families) depending on the position of the first two cystein residues. Chemokines mediate their proinflammatory effects by binding to a variety of specific receptors, belonging to the G protein-coupled superfamily of seven-transmembrane (serpentine) receptors. Some of this receptors serve as coreceptors for HIV-viruses, some of them could be expressed as markers preferentially in Th1 or Th2 subpopulations. This paper summarizes data on chemokines and their receptors, target cells and production in physiological and pathological conditions.
- MeSH
- chemokiny chemie klasifikace fyziologie MeSH
- lidé MeSH
- receptory chemokinů chemie klasifikace fyziologie MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- anglický abstrakt MeSH
- časopisecké články MeSH
- přehledy MeSH
- Názvy látek
- chemokiny MeSH
- receptory chemokinů MeSH
BACKGROUND: Extrinsic allergic alveolitis (EAA) and idiopathic pulmonary fibrosis (IPF) share the presence of varying degree interstitial involvement and fibrosis. Vascular changes were often reported to accompany the development of fibrosis. OBJECTIVES: The aim of our study was to examine the differences in angiostatic and angiogenic chemokine milieu in both diseases. Correlations between chemokine levels in bronchoalveolar lavage fluid (BALF), expression of chemokine receptors on CD4+ T cells (CXCR2, CXCR3) in BALF and HRCT pattern of the diseases were investigated. METHODS: Sixteen patients with chronic EAA and 8 with IPF were enrolled to the study. Concentrations of interleukin (IL)-8, epithelial neutrophil activating protein (ENA)-78, interferon-gamma-inducible protein (IP)-10 and interferon-inducible T cell alpha chemoattractant (I-TAC) in BALF supernatants were quantified using Fluorokine MultiAnalyte profiling. RESULTS: There was no significant difference in the BALF chemokine levels between the EAA and IPF group. IL-8 BALF concentrations correlate with the extent of fibrosis in both EAA and IPF (p<0.01). The IP-10 BALF concentrations do not correlate either with the HRCT alveolar or interstitial score and should be evaluated in the relationship with the disease course. CONCLUSIONS: Both IL-8 and ENA-78 probably play a different role in IPF and chronic EAA pathogenesis. While we suggest ENA-78 as the marker of at least partial reversibility of the lung impairment in the EAA patients, IL-8 could be rather an indicator of continuous exposition to provoking agent in EAA patients. IL-8 might serve as a potential marker of early phase of IPF.
- MeSH
- biologické markery MeSH
- bronchoalveolární lavážní tekutina imunologie MeSH
- chemokin CXCL10 analýza MeSH
- chemokin CXCL11 analýza MeSH
- chemokin CXCL5 analýza MeSH
- chemokiny analýza MeSH
- dospělí MeSH
- hypersenzitivní pneumonitida imunologie patologie MeSH
- idiopatická plicní fibróza imunologie patologie MeSH
- interleukin-8 analýza MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladý dospělý MeSH
- plíce imunologie patologie MeSH
- prognóza MeSH
- prospektivní studie MeSH
- receptory chemokinů analýza MeSH
- senioři nad 80 let MeSH
- senioři 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
- srovnávací studie MeSH
- Názvy látek
- biologické markery MeSH
- chemokin CXCL10 MeSH
- chemokin CXCL11 MeSH
- chemokin CXCL5 MeSH
- chemokiny MeSH
- CXCL10 protein, human MeSH Prohlížeč
- CXCL11 protein, human MeSH Prohlížeč
- interleukin-8 MeSH
- receptory chemokinů MeSH
Acyclic nucleoside phosphonates are novel class of clinically broadly used antivirotics effective against replication of both DNA viruses and retroviruses including human immunodeficiency virus (HIV). We have investigated their in vitro effects on immune defence mechanisms in human peripheral blood mononuclear cells, with the main emphasis on expression of cytokines which are able to suppress the entry of HIV in cells. Included in the study were prototype acyclic nucleoside phosphonates, i.e. 9-[2-(phosphonomethoxy)ethyl]adenine (PMEA; adefovir), 9-[2-(phosphonomethoxy)ethyl]-2,6-diaminopurine (PMEDAP), (R)-and (S)-enantiomers of 9-[2-(phosphonomethoxy)propyl]adenine [(R)-PMPA; tenofovir] and [(S)-PMPA], and of 9-[2-(phosphonomethoxy)propyl]-2,6-diaminopurine [(R)-PMPDAP] and [(S)-PMPDAP], and their N(6)-substituted derivatives. Some of the compounds were found to substantially enhance secretion of chemokines such as macrophage inflammatory protein-1alpha (MIP-alpha/CCL3), and "regulated on activation of normal T cell expressed and secreted" (RANTES/CCL5). Secretion of MIP-1beta/CCL4 was only marginally increased, whereas production of interleukin-16 (IL-16) and interferon-gamma (IFN-gamma) remained uninfluenced. The most effective proved to be the N(6)-cyclooctyl-PMEDAP, N(6)-isobutyl-PMEDAP, N(6)-pyrrolidino-PMEDAP, N(6)-cyclopropyl-(R)-PMPDAP, and N(6)-cyclopentyl-(R)-PMPDAP derivatives. Remarkably enhanced secretion of chemokines was reached within 2-4 h of the cell culture, and was observed at concentration of 2-5 microM. It may be suggested that acyclic nucleoside phosphonates represent a new generation of antivirotics with combined antimetabolic and therapeutically prospective immunostimulatory properties.
- MeSH
- adenin analogy a deriváty chemie farmakologie MeSH
- analýza rozptylu MeSH
- antiretrovirové látky farmakologie MeSH
- chemokin CCL3 metabolismus MeSH
- chemokin CCL4 metabolismus MeSH
- chemokin CCL5 MeSH
- chemokiny metabolismus MeSH
- dospělí MeSH
- interferon gama metabolismus MeSH
- kultivované buňky MeSH
- leukocyty mononukleární účinky léků metabolismus MeSH
- lidé středního věku MeSH
- lidé MeSH
- organofosfonáty chemie farmakologie MeSH
- stereoizomerie MeSH
- vztahy mezi strukturou a aktivitou 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
- adenin MeSH
- antiretrovirové látky MeSH
- CCL3 protein, human MeSH Prohlížeč
- CCL4 protein, human MeSH Prohlížeč
- chemokin CCL3 MeSH
- chemokin CCL4 MeSH
- chemokin CCL5 MeSH
- chemokiny MeSH
- interferon gama MeSH
- organofosfonáty MeSH
NK cells are an important component of natural immunity, which provides a defence response against viruses, bacterial and parasitic intracellular pathogens and tumour cells. NK cells are capable of rapid responses without prior sensitization and cytotoxic response is independent of the presence of the antigens of the major histocompatibility system. NK cells produce a number of cytokines (e.g. INF-gamma, GM-CSF and TNF-beta) and chemokines and in this way they regulate both the natural and acquired immune response. By contrast, NK cells are regulated both positively and negatively by cytokines and chemokines produced by other immune cells. Attention is focused on the possibility of influencing the tumour process by using cytokine- and chemokine-activated NK cells. In studies in mice models as well as in several clinical trials, it has been shown that the presence of cytotoxic cells in tumour stroma is associated with a more favourable prognosis of cancer.There is also plenty of evidence that in tumour stroma a number of cytokines and chemokines are produced which may have ambivalent effects.
- MeSH
- buňky NK imunologie MeSH
- chemokiny imunologie MeSH
- lidé MeSH
- nádory imunologie MeSH
- receptory chemokinů imunologie MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- anglický abstrakt MeSH
- časopisecké články MeSH
- přehledy MeSH
- Názvy látek
- chemokiny MeSH
- receptory chemokinů MeSH
BACKGROUND: Complex networks of chemokines are part of the immune reaction targeted against tumor cells. Chemokines influence cancer growth. It is unclear whether the concentrations of chemokines at the time of NSCLC (non-small cell lung cancer) diagnosis differ from healthy controls and reflect the extent of NSCLC. AIMS: To compare chemokine concentrations (CCL2, CCL8, CXCL12) in the plasma of patients with resectable NSCLC to those without cancer. To determine whether the chemokine concentrations differ relative to the stage of disease. METHODS: Sixty-nine patients undergoing surgery for proven/suspected NSCLC were enrolled. They underwent standard diagnostic and staging procedures to determine resectability, surgery was performed. Forty-two patients were diagnosed with NSCLC, while 27patients had benign lung lesions and functioned as the control group. Chemokine concentrations in peripheral blood were assessed using ELISA. Parametric statistics were used for the analysis of results. RESULTS: There were no differences in plasma chemokine concentrations in NSCLC patients compared to controls. CXCL12 concentrations correlated positively with tumor extent expressed as clinical stage, (mean values: stage I 5.08 ng/mL, SEM 0.59; stage II and IIIA 7.82 ng/mL; SEM 1.06; P=0.022). Patients with NSCLC stages II+IIIA had significantly higher CXCL12 concentrations than controls (mean values: stage II+IIIA 7.82 ng/mL; SEM 1.06; controls 5.3 ng/mL; SEM 0.46; P=0.017). CONCLUSION: CXCL12 was related to tumor growth and could potentially be used as a biomarker of advanced disease.
- Klíčová slova
- ELISA method, NSCLC, biomarker, chemokine CCL2, chemokine CCL8, chemokine CXCL12, peripheral blood, resectability,
- MeSH
- biologické markery MeSH
- chemokin CCL2 MeSH
- chemokin CCL8 MeSH
- chemokin CXCL12 MeSH
- chemokiny MeSH
- lidé MeSH
- nádory plic * chirurgie patologie MeSH
- nemalobuněčný karcinom plic * chirurgie patologie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- biologické markery MeSH
- CCL2 protein, human MeSH Prohlížeč
- CCL8 protein, human MeSH Prohlížeč
- chemokin CCL2 MeSH
- chemokin CCL8 MeSH
- chemokin CXCL12 MeSH
- chemokiny MeSH
- CXCL12 protein, human MeSH Prohlížeč
The effect of Ixodes ricinus tick saliva on the production of various cytokines and chemokines by mouse splenocytes was tested by a cytokine array. We demonstrated a strong upregulation of three chemokines, monocyte chemoattractant protein-1 (MCP-1), thymus-derived chemotactic agent 3 (TCA-3) and macrophage inflammatory protein 2 (MIP-2). MCP-1 could be induced by tick saliva itself. While TCA-3 and MIP-2 are engaged in Th2 polarization of the host immune response associated with tick feeding, MCP-1 may act as a histamine release factor, increasing blood flow into the feeding lesion thus facilitating tick engorgement in the late, rapid feeding phase.
- Klíčová slova
- Ixodes ricinus, MCP-1, Th2 response, chemokine, histamine, tick saliva,
- MeSH
- chemokin CCL1 imunologie MeSH
- chemokin CCL2 imunologie MeSH
- chemokin CXCL2 imunologie MeSH
- klíště imunologie MeSH
- myši inbrední C57BL MeSH
- myši MeSH
- organismy bez specifických patogenů MeSH
- sliny imunologie MeSH
- Th2 buňky imunologie MeSH
- uvolňování histaminu MeSH
- zvířata MeSH
- Check Tag
- myši MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- chemokin CCL1 MeSH
- chemokin CCL2 MeSH
- chemokin CXCL2 MeSH
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