- Publikační typ
- abstrakt z konference 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
- Publikační typ
- abstrakt z konference MeSH
M2 macrophages expressing CD163 are known to suppress immune responses but have been also found in biopsies of patients with chronic kidney allograft injury associated with interstitial fibrosis. The aim of our study was to evaluate the expression of CD163 in blood monocytes, precursors of tissue macrophages, in kidney allograft recipients with uncomplicated outcome (n=94) compared with those developing acute rejection (n=44). Blood samples were collected before the transplantation and at 1 week, 1 month and 1 year. The expression of CD163 increased during the first week after the transplantation not only in classical (CD14+CD16-) but also in intermediate (CD14+CD16+) and nonclassical (CD14lowCD16+) monocytes in all patients regardless of their rejection status. In patients developing acute rejection, higher pre-transplant expression of CD163 on blood monocytes was found. In vitro experiments confirmed strong induction of membrane CD163 on monocytes together with CD206 (an alternative marker of M2 macrophages) in response to IL-10. We assume from our data that dramatic upregulation of CD163 by peripheral blood monocytes may have a pathophysiological role in early phases after kidney allograft transplantation and high pre-transplant expression of CD163 on blood monocytes might be involved in events leading to acute rejection.
- MeSH
- alografty MeSH
- antigeny diferenciační myelomonocytární krev MeSH
- biologické markery krev MeSH
- CD antigeny krev MeSH
- dospělí MeSH
- interleukin-10 metabolismus MeSH
- lidé středního věku MeSH
- lidé MeSH
- makrofágy imunologie metabolismus MeSH
- mladiství MeSH
- mladý dospělý MeSH
- monocyty imunologie metabolismus MeSH
- receptory buněčného povrchu krev MeSH
- rejekce štěpu krev etiologie MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- transplantace ledvin * MeSH
- upregulace MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladiství MeSH
- mladý dospělý MeSH
- mužské pohlaví MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- Publikační typ
- abstrakt z konference MeSH
- Klíčová slova
- QFM, QuantiFERON Monitor,
- MeSH
- aktivace lymfocytů * účinky léků MeSH
- buněčná imunita * účinky léků MeSH
- dospělí MeSH
- idiopatické střevní záněty terapie MeSH
- imunologické testy klasifikace metody MeSH
- imunosupresiva MeSH
- imunosupresivní léčba MeSH
- infliximab terapeutické užití MeSH
- interferon gama krev účinky léků MeSH
- lidé středního věku MeSH
- lidé MeSH
- lymfocyty imunologie klasifikace účinky léků MeSH
- melfalan terapeutické užití MeSH
- mnohočetný myelom terapie MeSH
- senioři MeSH
- transplantace hematopoetických kmenových buněk MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- srovnávací studie MeSH
BACKGROUND The aim of the study was to investigate the role of von Willebrand factor (vWF), the vWF-cleaving protease, ADAMTS13, the composition of thrombus, and patient outcome following mechanical cerebral artery thrombectomy in patients with acute ischemic stroke. MATERIAL AND METHODS A prospective cohort study included 131 patients with ischemic stroke (<6 hours) with or without intravenous thrombolysis. Interventional procedure parameters, hemocoagulation markers, vWF, ADAMTS13, and histological examination of the extracted thrombi were performed. The National Institutes of Health Stroke Scale (NIHSS) score was used on hospital admission, after 24 hours, at day 7; the three-month modified Rankin Scale score was used. RESULTS Mechanical thrombectomy resulted in a Treatment in Cerebral Ischemia (TICI) score of 2-3, with recanalization in 89% of patients. Intravenous thrombolysis was used in 101 (78%). Patients with and without intravenous thrombolysis therapy had a good clinical outcome (score 0-2) in 47% of cases (P=0.459) using the three-month modified Rankin Scale. Patients with a National Institutes of Health Stroke Scale (NIHSS) score ≥15 had significantly increased vWF levels (P=0.003), and a significantly increased vWF: ADAMTS13 ratio (P=0.038) on hospital admission. Significant correlation coefficients were found for plasma vWF and thrombo-embolus vWF (r=0.32), platelet (r=0.24), and fibrin (r=0.26) levels. In the removed thrombus, vWF levels were significantly correlated with platelet count (r=0.53), CD31-positive cells (r=0.38), and fibrin (r=0.48). CONCLUSIONS In patients with acute ischemic stroke, mechanical cerebral artery thrombectomy resulted in a good clinical outcome in 47% of cases, with and without intravenous thrombolysis therapy.
- MeSH
- arteriae cerebrales metabolismus patologie MeSH
- cévní mozková příhoda krev metabolismus chirurgie MeSH
- demografie MeSH
- hemokoagulace MeSH
- ischemie mozku krev metabolismus chirurgie MeSH
- lidé středního věku MeSH
- lidé MeSH
- protein ADAMTS13 metabolismus MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- trombektomie * MeSH
- trombóza krev imunologie metabolismus MeSH
- von Willebrandův faktor metabolismus MeSH
- výsledek terapie MeSH
- zánět patologie MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
BACKGROUND The immune system may have a role in the pathogenesis of autism spectrum disorder (ASD), including typical and atypical autism. The aim of this study was to determine whether a cytokine and growth factor panel could be identified for the diagnosis and prognosis in children with ASD, including typical and atypical autism. MATERIAL AND METHODS This study included 26 children with ASD (typical or atypical) and 11 of their siblings who did not have ASD. A panel of ten serum cytokines and growth factors were investigated using addressable laser bead assay (ALBIA) and enzyme-linked immunosorbent assay (ELISA) kits. Results were correlated with scores using the Childhood Autism Rating Scale (CARS) and Autism Diagnostic Observation Schedule (ADOS) for the children with ASD and compared with the findings from their siblings without ASD. RESULTS There were no statistically significant differences in serum cytokine and growth factor levels between children with ASD and their siblings. The scores using CARS and ADOS were significantly greater in children with typical autism compared with children with atypical autism as part of the ASD spectrum. Serum levels of cytokines and growth factors showed a positive correlation with CARS and ADOS scores but differed between children with typical and atypical autism and their siblings. CONCLUSIONS The findings of this study showed that serum measurement of appropriately selected panels of cytokines and growth factors might have a role in the diagnosis of ASD.
- Publikační typ
- abstrakt z konference MeSH
Macrolide antibiotics such as azithromycin or clarithromycin are known to have potent anti-inflammatory and immunomodulatory effects but these properties cannot be widely used due to a risk of bacterial resistance. We studied another polyketide antibiotic, structurally related manumycin A known as a streptomycete derived farnesyltransferase inhibitor with limited antibacterial effects, with respect to its potential regulation of mRNA expression of several genes associated with proinflammatory responses. Downregulation of mRNA for IL-6, TLR-8, IL-1 beta and IL-10 was found in THP-1 cells after 4h stimulation with TNF alpha in the presence of manumycin A and downregulated TLR-8 and EGR-1 genes were observed after 8h. Among the genes upregulated in response to manumycin were HMOX-1, TNFRSF10A, IL-1R1, TICAM2, NLRP12 after 4h and only IL-1R1 after 8h. Furthermore, manumycin A was found to inhibit IL-1beta, IL-6, and IL-8 production in TNF alpha stimulated THP-1 cells and peripheral blood monocytes in a dose dependent manner (0.25-1 μM of manumycin A) without affecting cell viability. Cell viability of blood monocytes decreased by about 30% at manumycin A doses of 2-5 μM. Manumycin A also inhibited IL-18 release from THP-1 cells, while in cultures of blood monocytes, this cytokine was not detectable. That manumycin A mediated downregulation of proinflammatory genes in human monocytes confirmed by a measurement of cytokine levels in culture supernatants, together with a very limited effect on cell viability, might suggest potential anti-inflammatory properties of this polyketide antibiotic.
- MeSH
- antibakteriální látky farmakologie MeSH
- antiflogistika farmakologie MeSH
- buněčné linie MeSH
- cytokiny genetika metabolismus MeSH
- imunomodulace MeSH
- lidé MeSH
- messenger RNA genetika MeSH
- monocyty účinky léků imunologie MeSH
- polyeny farmakologie MeSH
- polynenasycené alkamidy farmakologie MeSH
- protein 1 časné růstové odpovědi genetika metabolismus MeSH
- receptory interleukinu-1 genetika metabolismus MeSH
- regulace genové exprese účinky léků MeSH
- TNF-alfa metabolismus MeSH
- toll-like receptor 8 genetika metabolismus MeSH
- zánět farmakoterapie imunologie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
