- Publikační typ
- abstrakt z konference MeSH
- Publikační typ
- abstrakt z konference MeSH
Závěrečná zpráva o řešení grantu Interní grantové agentury MZ ČR
1 svazek : ilustrace, tabulky ; 30 cm
1.The project will investigate mRNA & protein expression profile (EP) of selected molecules, related to pro-fibrotic processes in diffuse lung diseases (DLDs). 2. The EP of chemokines, cytokines and other regulatory molecules contributing to activation of fibroblasts, extracellular matrix protein deposition and regulation of inflammation will be investigated. 3. Beside contribution to knowledge on pathomechanisms, the knowledge of EP associated with DLDs may contribute to earlier and more precise assessment of diagnosis, prediction of disease outcome, control of therapeutic response and staging of patients. 4. This project will also suggest new candidates for genetic studies in DLDs and for its therapy.
Projekt je zaměřen na analýzu expresních profilů (RNA, protein) vybraných molekul účastnících se profibrotizačních procesů u pacientů s difúzními plicními onemocněními (DPO). Budeme sledovat EP chemokinů/cytokinů a dalších molekul podílejících se na aktivaci fibroblastů, tvorbě proteinů extracelulární matrix a regulaci zánětu. Znalost EP přispěje k objasnění patogenetických mechanizmů fibrotizace, přispěje k rozšíření klasifikačního schématu fibróz charakteristických velmi špatnou prognózou, umožní stratifikovat pacienty s rizikem fibrotizace a sledovat léčebnou odpověď. Projekt dále umožní určit kandidátní molekuly pro následnou analýzu genetických mechanizmů a navrhnout cíle pro budoucí terapii.
- MeSH
- bronchoalveolární lavážní tekutina MeSH
- chemokiny analýza MeSH
- cytokiny analýza MeSH
- exprese genu MeSH
- individualizovaná medicína MeSH
- intersticiální plicní nemoci MeSH
- mikro RNA analýza MeSH
- plicní fibróza MeSH
- plicní sarkoidóza MeSH
- polymorfismus genetický MeSH
- progrese nemoci MeSH
- Konspekt
- Biochemie. Molekulární biologie. Biofyzika
- NLK Obory
- biologie
- genetika, lékařská genetika
- pneumologie a ftizeologie
- NLK Publikační typ
- závěrečné zprávy o řešení grantu IGA MZ ČR
Idiopatická plicní fibróza (IPF) patří mezi nejobtížněji léčitelné a zároveň prognosticky nejzávažnější plicní onemocnění. Současný výzkum naznačuje, že klíčovou roli v patogenezi tohoto onemocnění hrají mimo jiné chemokinové receptory a jejich ligandy nazývané chemokiny (chemotaktické cytokiny), které se významně podílejí na zánětlivých a fibrotizujících procesech, ale také se účastní reparace, regenerace a remodelace plicní tkáně. Výsledky studií zvířecích modelů zacílených na chemokinové receptory a jejich působení u IPF naznačují, že by se chemokinové receptory mohly stát atraktivními terapeutickými cíli nejen u tohoto onemocnění, ale také v léčbě řady dalších plicních nemocí. Cílem tohoto sdělení bylo shrnout současné poznatky o úloze chemokinových receptorů a jejich ligandů, získaných převážně na studiích u zvířecích modelů plicní fibrózy, a popsat perspektivy jejich terapeutického využití u IPF.
Idiopathic pulmonary fibrosis (IPF) is one of the moslst difficult to tieat and prognostically most severe lung disease. Current research suggests that chemokine receptors and their ligands called chemokines (chemotactic cytokines) play a key role in the pathogenesis of this disease, contributing to the inflammatory and profibrotic processes as well as to the regulation of lung tissue repair, regeneration and remodeling. Results of studies in animal models focused on chemokine receptors and their role in pulmonary fibrosis suggest that the chemokine receptors may become attractive therapeutic targets not only in IPF, but also in the treatment of other lung diseases. The aims of this review were to summarize current knowledge on the role of chemokine receptors and their ligands in pulmonary fibrosis, currently investigated mainly in animal models of pulmonary fibrosis, and to delineate the prospects for their use in the treatment of IPF.
- Publikační typ
- abstrakt z konference MeSH
- Publikační typ
- abstrakt z konference MeSH
PURPOSE OF THE STUDY: Aseptic loosening (AL) and periprosthetic osteolysis (PPOL) in total hip (THA) and knee (TKA) arthroplasty are linked to an inflammatory process initiated by wear debris released from artificial joints. There is still limited information about the contribution of Toll-like receptors (TLRs) and distinct regulatory cytokines to AL/PPOL in both joints. METHODS: In this study, we investigated mRNA expression of TLR-1,-2,-4 and cytokines/receptors (IL-2,-2R,-10,-10R, TGFb1) in pseudosynovial tissue obtained from 55 patients with aseptically failed THAs/TKAs and 37 control patients with hip/knee primary osteoarthritis (OA) using quantitative RT-PCR. Immunohistochemical staining was used to detect the corresponding proteins. Non-parametric Kruskal-Wallis and Mann-Whitney tests were used to determine differences between the patient groups. RESULTS: When comparing expression profiles between patients with aseptically failed THA and TKA, higher amounts of TLR-1,- 2,-4 and IL-2R mRNA transcripts were detected in THA patients. The mRNA expression of studied molecules (TLR-1,-2,-4, IL-2, IL-10, IL-2R, IL-10R, TGFb1) did not differ between THA and OA hip tissues. Lower mRNA expression of TLR-1,-2,- 4, IL-10, and IL-10R was detected in TKA when compared to control knee OA. Similar mRNA profiles of IL-2, IL-2R, and TGFb1 were observed in TKA and knee OA. Using immunohistochemistry, we detected low expression of TLR-1 protein in failed THA/TKA, whereas TLR-2 protein levels were higher in TKA/THA patients than in OA controls. High individual variability in TLR-4 protein levels was detected among patients with aseptically loosened THA and TKA. IL-10 protein levels were similar in THA and TKA patient subgroups and control subjects, whereas IL-10R protein level was higher in failed TKAs and OA controls than in THAs. No difference in IL-2 protein levels was detected between patients with THA/TKA and those with OA. DISCUSSION: Our data indicate close similarity between the expression patterns in aseptically failed THA and TKA. However, certain differences were observed which also suggest unique pathways associated with the end-stage of aseptic loosening in THA and TKA. For instance, differences in the size, shape and load of polyethylene particles between THA and TKA could play some role. The composition of THA and TKA and differences in terms of mechanical forces might also be involved. CONCLUSIONS: This is the fist study comparing the gene expression profile of a particular set of innate immunity regulatory molecules between tissues from aseptically failed THA and TKA. Low expression of TLR-1,-2,-4 and cytokines/receptors (IL-2, IL-2R, IL-10, IL-10R, and TGFb1) was observed in pseudosynovial tissues obtained from aseptically failed THAs and TKAs. Higher amount of TLR transcripts was detected in THA as compared to TKA. These findings indicate certain differences in the mechanism of aseptic loosening occurring at the site of THA and TKA. Further research is warranted.
- MeSH
- cytokiny biosyntéza genetika MeSH
- exprese genu imunologie MeSH
- kyčelní protézy MeSH
- lidé MeSH
- messenger RNA genetika MeSH
- náhrada kyčelního kloubu MeSH
- přirozená imunita MeSH
- protézy kolene * MeSH
- receptory cytokinové biosyntéza genetika MeSH
- reoperace MeSH
- selhání protézy * MeSH
- studie případů a kontrol MeSH
- synoviální membrána imunologie MeSH
- toll-like receptory biosyntéza genetika MeSH
- totální endoprotéza kolene * MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- anglický abstrakt MeSH
- časopisecké články MeSH
Sarcoidosis is an inflammatory granulomatous disease with unknown etiology driven by cytokines and chemokines. There is limited information regarding the regulation of cytokine/chemokine-receptor network in bronchoalveolar lavage (BAL) cells in pulmonary sarcoidosis, suggesting contribution of miRNAs and transcription factors. We therefore investigated gene expression of 25 inflammation-related miRNAs, 27 cytokines/chemokines/receptors, and a Th1-transcription factor T-bet in unseparated BAL cells obtained from 48 sarcoidosis patients and 14 control subjects using quantitative RT-PCR. We then examined both miRNA-mRNA expressions to enrich relevant relationships. This first study on miRNAs in sarcoid BAL cells detected deregulation of miR-146a, miR-150, miR-202, miR-204, and miR-222 expression comparing to controls. Subanalysis revealed higher number of miR-155, let-7c transcripts in progressing (n = 20) comparing to regressing (n = 28) disease as assessed by 2-year follow-up. Correlation network analysis revealed relationships between microRNAs, transcription factor T-bet, and deregulated cytokine/chemokine-receptor network in sarcoid BAL cells. Furthermore, T-bet showed more pronounced regulatory capability to sarcoidosis-associated cytokines/chemokines/receptors than miRNAs, which may function rather as "fine-tuners" of cytokine/chemokine expression. Our correlation network study implies contribution of both microRNAs and Th1-transcription factor T-bet to the regulation of cytokine/chemokine-receptor network in BAL cells in sarcoidosis. Functional studies are needed to confirm biological relevance of the obtained relationships.
- MeSH
- dospělí MeSH
- genové regulační sítě * MeSH
- lidé středního věku MeSH
- lidé MeSH
- messenger RNA analýza MeSH
- mikro RNA fyziologie MeSH
- plicní sarkoidóza imunologie MeSH
- proteiny T-boxu fyziologie MeSH
- receptory chemokinů genetika MeSH
- receptory cytokinové 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
