Rheumatoid arthritis (RA) and its animal model adjuvant arthritis (AA) are inflammatory diseases characterized by chronic inflammation, systemic oxidative stress and disturbed mitochondrial bioenergetics of skeletal muscle. The present study aimed to evaluate the effects of coenzyme Q10 - CoQ10 (100 mg/kg b.w.), omega-3-polyunsaturated fatty acids - omega-3-PUFA (400 mg/kg b.w.) and their combined treatment in AA on impaired skeletal muscle mitochondrial bioenergetics, inflammation and changes in levels CoQ9 and CoQ10 in plasma. Markers of inflammation (C-reactive protein, monocyte-chemotactic protein-1), antioxidant capacity of plasma, respiratory chain parameters of skeletal muscle mitochondria and concentrations of CoQ9 and CoQ10 in plasma and in muscle tissue were estimated. Treatment of the arthritic rats with CoQ10, omega-3-PUFA alone and in combination partially reduced markers of inflammation and increased antioxidant capacity of plasma, significantly increased concentrations of coenzyme Q in mitochondria and improved mitochondrial function in the skeletal muscle. Combined treatment has similar effect on the mitochondrial function as monotherapies; however, it has affected inflammation and antioxidant status more intensively than monotherapies. Long-term supplementary administration of coenzyme Q10 and omega-3-PUFA and especially their combination is able to restore the impaired mitochondrial bioenergetics and antioxidant status in AA.
- MeSH
- antioxidancia metabolismus MeSH
- artritida experimentální krev dietoterapie MeSH
- C-reaktivní protein metabolismus MeSH
- chemokin CCL2 krev MeSH
- kyseliny mastné omega-3 terapeutické užití MeSH
- potkani inbrední LEW MeSH
- potravní doplňky MeSH
- revmatoidní artritida krev dietoterapie MeSH
- svalové mitochondrie metabolismus MeSH
- ubichinon analogy a deriváty metabolismus terapeutické užití MeSH
- zvířata MeSH
- Check Tag
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- hodnotící studie MeSH
Kidney allograft transplantation improved the prognosis and quality of life of patients with end-stage renal diseases but the occurrence of acute rejection represents a limitation of the final outcome. Noninvasive biomarkers are needed as well as further advancements in the understanding of immune mechanisms of reaction to the allograft. Our study of 138 patients focused on one-year monitoring of serum concentrations of 12 chemokines regulating the recruitment of different immune cells into transplanted allograft and on in vitro regulation of the same chemokines release by interactions of renal proximal epithelial cells with monocyte/macrophage cell line stimulated with TNF alpha. In a group of 44 patients with acute rejection, higher serum pretransplant levels of CXCL1, CXCL5, CXCL6, CCL2, CCL21, and particularly CXCL10 and CX3CL1(both p < 0.001) were found suggesting their higher proinflammatory status as compared to subjects with the uncomplicated outcome. In samples collected at the day of biopsy positive for acute rejection, chemokines CXCL9 and CXCL11 attracting preferentially Th1 lymphocytes were found to be upregulated. In our in vitro model with TNF alpha induction, renal proximal epithelial cells seemed to be a more potent source of chemokines attracting neutrophils as compared to monocyte/macrophage cell line but the coculture of these cells potentiated release of neutrophilic chemokines CXCL5 and CXCL6. Similar augmentation of chemokine production was found also in the case of CCL2. On the other hand, adding of monocytes/macrophages to a culture of renal epithelial cells suppressed the release of CXCL10 and CXCL11 attracting T lymphocytes. We assume from our data that in kidney allograft transplantation, chemokines attracting neutrophils, T lymphocytes, and monocytes are induced simultaneously and measurement some of them in combination might be used as biomarkers of acute rejection. Mutual cell-cell interactions of immune cells with renal parenchyma seem to be important for fine regulation of chemokine release.
- MeSH
- alografty MeSH
- chemokin CCL2 krev MeSH
- chemokin CCL21 krev MeSH
- chemokin CX3CL1 krev MeSH
- chemokin CXCL1 krev MeSH
- chemokin CXCL10 krev MeSH
- chemokin CXCL11 krev MeSH
- chemokin CXCL5 krev MeSH
- chemokin CXCL6 krev MeSH
- chemokin CXCL9 krev MeSH
- chemokiny krev MeSH
- kvalita života MeSH
- lidé MeSH
- rejekce štěpu krev imunologie MeSH
- Th1 buňky metabolismus MeSH
- transplantace ledvin škodlivé účinky MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
BACKGROUND: The development of hand osteoarthritis (HOA) and its progression into the erosive subset are unclear, but inflammation is suspected to be the main source. To verify the involvement of inflammation in HOA pathogenesis, we evaluate serum inflammatory mediators and their association with HOA-related clinical features in patients. METHODS: 153 participants (50 non-erosive HOA patients, 54 erosive HOA patients, and 49 healthy control subjects) were included in this study. All patients underwent clinical examination, which included assessment of tender and swollen small hand joints, ultrasound (US) examination, and self-reported measures (e.g., AUSCAN or algofunctional indexes). Serum inflammatory mediators were quantified using human cytokine 27-plex immunoassay. We employed linear modelling, correlation analysis, and resampling statistics to evaluate the association of these mediators to HOA. RESULTS: We identified increased levels of nine inflammatory mediators (e.g., eotaxin, monocyte chemoattractant protein 1, interleukin-8, and tumour necrosis factor) in HOA patients compared to healthy controls. Increased mediators correlated with ultrasound findings as well as with clinically tender and swollen joint counts in patients with erosive HOA. However, none of the mediators distinguished between erosive and non-erosive HOA subtypes. CONCLUSION: Our findings support the hypothesis on the involvement of inflammation in HOA.
- MeSH
- chemokin CCL11 krev MeSH
- chemokin CCL2 krev MeSH
- chemokiny krev MeSH
- cytokiny krev MeSH
- interleukin-8 krev MeSH
- lidé středního věku MeSH
- lidé MeSH
- osteoartróza krev patologie MeSH
- progrese nemoci MeSH
- ruka patofyziologie MeSH
- senioři MeSH
- TNF-alfa krev MeSH
- zánět krev patofyziologie MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
BACKGROUND: The recognition of active inflammation in the central nervous system (CNS) in the absence of infectious agents is challenging. The present study aimed to determine the diagnostic relevance of five selected chemo/cytokines in the recognition of CNS inflammation and in the context of traditional cerebrospinal fluid (CSF) biomarkers (white blood cell [WBC] counts, oligoclonal bands, protein levels, CSF/serum albumin ratios) and clinical diagnoses. METHODS: C-C and C-X-C motif ligands (CCL2, CXCL8, 10 and 13) and interleukin (IL) 6 levels in the CSF and serum from 37 control and 87 symptomatic children with ten different (mostly noninfectious) inflammatory CNS disorders (16 of which had follow-up samples after recovery) were determined using Luminex multiple bead technology and software. Nonparametric tests were used; p < 0.05 was considered statistically significant. Receiver operating characteristic curves were constructed to analyze controls and 1) all symptomatic samples or 2) symptomatic samples without CSF pleocytosis. RESULTS: Compared with the control CSF samples, levels of all investigated chemo/cytokines were increased in symptomatic CSF samples, and only IL-6 remained elevated in recovery samples (p ≤ 0.001). CSF CXCL-13 levels (> 10.9 pg/mL) were the best individual discriminatory criterion to differentiate neuroinflammation (specificity/sensitivity: 97/72% and 97/61% for samples without pleocytosis), followed by CSF WBC counts (specificity/sensitivity: 97/62%). The clinical utility of the remaining CSF chemo/cytokine levels was determined in descending order of sensitivities corresponding to thresholds that ensured 97% specificity for neuroinflammation in samples without pleocytosis (pg/mL; sensitivity %): IL-6 (3.8; 34), CXCL8 (32; 26), CXCL10 (317; 24) and CCL2 (387; 10). Different diagnosis-related patterns of CSF chemo/cytokines were observed. CONCLUSIONS: The increased CSF level of CXCL13 was the marker with the greatest predictive utility for the general recognition of neuroinflammation among all of the individually investigated biomarkers. The potential clinical utility of chemo/cytokines in the differential diagnosis of neuroinflammatory diseases was identified.
- MeSH
- biologické markery krev mozkomíšní mok MeSH
- chemokin CCL2 krev mozkomíšní mok MeSH
- chemokin CXCL10 krev mozkomíšní mok MeSH
- chemokin CXCL13 krev mozkomíšní mok MeSH
- chemokiny krev mozkomíšní mok MeSH
- dítě MeSH
- interleukin-6 krev mozkomíšní mok MeSH
- interleukin-8 krev mozkomíšní mok MeSH
- krevní obraz MeSH
- lidé MeSH
- mladiství MeSH
- nemoci centrálního nervového systému mozkomíšní mok diagnóza imunologie MeSH
- předškolní dítě MeSH
- ROC křivka MeSH
- Check Tag
- dítě MeSH
- lidé MeSH
- mladiství MeSH
- mužské pohlaví MeSH
- předškolní dítě MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Exposure to hypoxia, leading to hypoxic pulmonary hypertension (HPH), is associated with activation of alveolar macrophages (AM). However, it remains unclear how AM participate in this process. There are studies which imply that the AM product monocyte chemoattractant protein-1 (MCP-1) plays an important role. Thus we tested: 1. if the selective elimination of AM attenuates HPH in rats, 2. the correlation of MCP-1 plasmatic concentrations with the presence and absence of AM during exposure to hypoxia, 3. the direct influence of hypoxia on MCP-1 production in isolated AM. We found that experimental depletion of AM attenuated the chronic hypoxia-induced increase in mean pulmonary arterial pressure, but did not affect the serum MCP-1 concentrations. Furthermore, the MCP-1 production by AM in vitro was unaffected by hypoxia. Thus we conclude that AM play a significant role in the mechanism of HPH, but MCP-1 release from these cells is most likely not involved in this process. The increase of MCP-1 accompanying the development of HPH probably originates from other sources than AM.
- MeSH
- alveolární makrofágy sekrece MeSH
- chemokin CCL2 krev MeSH
- dichlormethylendifosfonát terapeutické užití MeSH
- hypoxie komplikace MeSH
- plicní hypertenze imunologie prevence a kontrola MeSH
- potkani Wistar MeSH
- zvířata MeSH
- Check Tag
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
Tumor models are essential for basic anticancer research and development of novel therapies. In this study, we used a rat sarcoma model in which subcutaneous tumor develops after D6 cell inoculation. The aim of the current study was to analyze changes in haematological parameters, immune cell sub-populations and cytokine profiling during tumor growth, after tumor excision and after second inoculation of D6 cells. Tumor progression was found to be associated with an increased number of leukocytes and increased proportion of CD11b+ cells in peripheral blood. Serum concentration of chemokine (c-c motif) ligand 2, L-selectin and intra cellular adhesion molecule-1 also increased with growing tumor. However, the proportion of CD4+, CD8+ and MHC II+ cells decreased with growth of tumors. After tumor excision, all these parameters returned to pre-inoculation levels and did not change even after a second inoculation of D6 cells. Moreover, absence of secondary tumors after second inoculation of D6 cells gives an insight into development of antitumor immunity stimulated by primary tumor.
- MeSH
- antigeny CD11b krev MeSH
- chemokin CCL2 krev MeSH
- experimentální sarkom krev patologie MeSH
- krysa rodu rattus MeSH
- leukocytóza MeSH
- potkani inbrední LEW MeSH
- progrese nemoci MeSH
- průtoková cytometrie MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Our prospective study analyzed selected adipocytokines: adiponectin (ADPN), leptin, visfatin, and asymmetric dimethylarginine (ADMA) in the plasma of renal transplant recipients previously treated by peritoneal dialysis and hemodialysis. A total of 70 patients were on follow-up for 12 months after transplantation. Of these, 30 patients (group I) developed obesity, and 40 patients were nonobese (group II). All were receiving standard immunosuppressive therapy (cyclosporine A or tacrolimus and mycophenolate mofetil, with prednisone added in the early posttransplant period) and did not differ statistically in HLA typing, age, sex, duration of previous dialysis, history of cardiovascular disease, and rate of rejection episodes. At the end of the study period, there were significant differences between groups I and II (t test, analysis of variance) in plasma: ADPN, 22.30 ± 10.2 versus 14.3 ± 7.2 μg/mL; visfatin, 1.7 ± 0.1 versus 1.2 ± 0.1 ng/mL; ADMA, 3.60 ± 0.47 versus 2.10 ± 0.36 μmol/L; P < .01; leptin, 55.6 ± 10.2 versus 25.6 ± 8.3 ng/L; P < .01 (P < .02). In conclusion, an increase of body fat after renal transplantation was associated with an increase of ADMA and leptin, TNF-α, MCP-1, and visfatin and decrease of adiponectin. Our study documented there was now long-term beneficial metabolic effect of peritoneal dialysis in developing posttransplant obesity.
- MeSH
- adiponektin krev MeSH
- arginin analogy a deriváty krev MeSH
- chemokin CCL2 krev MeSH
- dialýza ledvin MeSH
- imunosupresiva aplikace a dávkování MeSH
- leptin krev MeSH
- lidé MeSH
- nikotinamidfosforibosyltransferasa krev MeSH
- obezita krev etiologie metabolismus MeSH
- peritoneální dialýza MeSH
- prospektivní studie MeSH
- svaly metabolismus MeSH
- TNF-alfa krev MeSH
- transplantace ledvin škodlivé účinky MeSH
- tuková tkáň metabolismus MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Cíle práce: Formování amyloidových depozit probíhá především v monocytech a makrofázích. Z těchto důvodů lze předpokládat, Že některé polymoďizmy genů pro MCP-1 (monocyte chemoatracttant protein-1) a MIP-1 α (macrophage inflammatory protein-1 alpha) mohou ovlivňovat vznik sekundární (AA) amyloidózy. Cílem práce bylo stanovit vybrané polymorfizmy těchto genů a sérové koncentrace proteinů, které kódují, v populaci českých pacientů s AA amyloidózou a v kontrolních skupinách. Metodika: Byla zjišťována incidence jednotlivých genotypů ve vybraných polymorfizmech genů pro MCP-1 a MIP-1α. Byly stanoveny sérové koncentrace MCP-1 a MlP-1α a zkoumána závislost koncentrací daných cytokinů na polymorfizmech příslušných genů. Stanovení se týkala nemocných s AA amyloidózou (n = 43), pacientů s revmatoidní artritidou (RA) bez amyloidózy (n = 50) a kontrolní skupiny zdravých dobrovolníků (n = 100). Výsledky: Nebyly nalezeny statisticky významné rozdíly v zastoupení zkoumaných genotypů. Významně zvýšená (p < 0,05) byla sérová koncentrace MCP-1 ve skupině nemocných s AA amyloidózou proti skupině nemocných s RA. Zřetelně, i když ne statisticky významně, byly vyšší i koncentrace MIP u obou skupin nemocných proti kontrolní skupině zdravých dobrovolníků. Závěr: Námi zjištěné signifikantně vyšší sérové koncentrace MCP-1 ve skupině nemocných s AA amyloidózou proti skupině nemocných s RA by mohly poukazovat na zvýšenou aktivaci monocytů jako rizikového faktoru pro rozvoj onemocnění. To by mohlo mít i své terapeutické konsekvence - dřívější a razantnější léčbu onemocnění predisponujících ke vzniku AA amyloidózy u pacientů s příslušným genotypem. Potřebné je ale tyto závěry ověřit ve větších souborech nemocných.
Aim of work: Formation of amyloid deposits is localized mainly in monocytes and macrophages. Thus we may suppose influence of some polymorphisms of MCP-1 (monocyte chemoatracttant protein-1) and MIP-1 α (macrophage inflammatory protein-1 alpha) genes. The aim of this work was to determine these polymorphisms and to measure serum levels of proteins which are coded by these gene s in population of Czech patients with AA amyloidosis and control groups. Methods: The incidence of single genotypes MCP-1 and MIP-1 α genes was investigated. Serum levels of MCP-1 and MIP-1a were measured and potential relation between serum levels and genotypes was analyzed. All examinations were performed in patients wi th AA amyloidosis (n = 43), rheumatoid arthritis (n = RA) without amyloidosis and control group of healthy volunteers (n = 100). Results: No statistically significant differences in distribution of the investigated genotypes were found. Serum concentration of MCP- 1 was statistically significantly higher in AA amyloidosis group compared to RA group (p < 0,05). Concentrations of MIP were mark edly (but not statistically significantly) higher in both groups of patients compared to healthy controls. Conclusions: Our findings of significantly higher serum concentrations of MCP-1 in the AA amyloidosis group compared to RA group could advert to increased monocyte activation as a risk factor for development of AA amyloidosis. This could have also therapeu tic consequence – earlier and more assertive therapy of underlying diseases in patients with appropriate genotype in order to preve nt or interfere with occurrence of AA amyloidosis. Further studies in larger populations of patients are warranted.
- MeSH
- amyloidóza genetika krev MeSH
- chemokin CCL2 diagnostické užití genetika krev MeSH
- chemokin CCL3 diagnostické užití genetika krev MeSH
- chemokiny genetika krev MeSH
- dospělí MeSH
- financování organizované MeSH
- lidé středního věku MeSH
- lidé MeSH
- polymorfismus genetický genetika MeSH
- revmatoidní artritida genetika krev MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- srovnávací studie 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
Poznatky získané v posledních letech defi nují aterosklerózu jako chronické systémové zánětlivé onemocnění, které je charakterizováno degenerativními změnami a extracelulární akumulací lipidů. Zánět je důležitým patogenetickým mechanismem aterosklerózy, jejíž klinické projevy zahrnují onemocnění různé lokalizace a závažnosti. V procesu aterogeneze hrají klíčovou úlohu chemotaktické cytokiny a jejich receptory. Expresi a funkci těchto molekul ovlivňuje variabilita (polymorfi smy) genů, které je kódují. Snahou badatelů v translačním výzkumu je na základě nových znalostí patobiologie kardiovaskulárních onemocnění rozšířit současné spektrum vyšetřovaných parametrů o nové ukazatele, které by pomohly upřesnit míru rizika vzniku a progrese onemocnění. Jednou z cest k vytčenému cíli je studium kandidátních molekul uplatňujících se v patogenezi aterosklerózy, diskutovanou kandidátní molekulou je také mononukleární chemoatraktant MCP-1 (CCL2) a jeho receptor CCR2.
Atherosclerosis has been defi ned as systemic, chronic infl ammatory disease characterized by degenerative processes and extracellular accumulation of lipids. Infl ammation is important pathogenetic mechanism of atherosclerosis whose clinical manifestations comprise diseases of distinct location. Chemotactic cytokines and their receptors play key role in atherogenesis. Expression and function of these molecules is infl uenced by variability (polymorphisms) in their encoding genes. Translational research in pathobiology of cardiovascular disorders aims at extending the current spectrum of laboratory parameters with new markers, which could help us to defi ne the patients at risk more precisely and to determine disease course more accurately. Investigation of atherosclerosis candidate molecules is one of the possible routes to this aim. Mononuclear chemoattractant MCP-1 (CCL2) and its receptor CCR2 represent such molecules.
- Klíčová slova
- mononukleární chemoatraktant MCP-1 (CCL2), receptor CCR2,
- MeSH
- angina pectoris MeSH
- ateroskleróza genetika imunologie MeSH
- chemokin CCL2 genetika krev MeSH
- infarkt myokardu MeSH
- klinické zkoušky jako téma MeSH
- lidé MeSH
- mediátory zánětu MeSH
- polymorfismus genetický MeSH
- receptory CCR2 MeSH
- zánět MeSH
- Check Tag
- lidé MeSH
