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
- MeSH
- dítě MeSH
- lidé MeSH
- nádorové biomarkery biosyntéza genetika MeSH
- pre-B-buněčná leukemie diagnóza genetika metabolismus MeSH
- předškolní dítě MeSH
- receptory cytokinové biosyntéza genetika MeSH
- regulace genové exprese u leukemie * MeSH
- signální transdukce fyziologie MeSH
- Check Tag
- dítě MeSH
- lidé MeSH
- mužské pohlaví MeSH
- předškolní dítě MeSH
- ženské pohlaví MeSH
- Publikační typ
- dopisy MeSH
- klinické zkoušky MeSH
- multicentrická studie MeSH
- práce podpořená grantem MeSH
BACKGROUND: The differences in total hip arthroplasty (THA) survivorship may be influenced by individual susceptibility to periprosthetic osteolysis. This may be driven by functional polymorphisms in the genes for cytokines and cytokine receptors involved in the development of osteolysis in THA, thereby having an effect on the individual's phenotype. METHODS: We performed a study on 22 single-nucleotide polymorphisms (SNPs) for 11 cytokines and two cytokine receptor candidate genes for association with severity of acetabular osteolysis and risk to failure in THA. Samples from 205 unrelated Caucasian patients with cementless type THA (ABG 1) were investigated. Distribution of investigated SNP variants between the groups of mild and severe acetabular osteolysis was determined by univariate and multivariate analysis. Time-dependent output variables were analyzed by the Cox hazards model. RESULTS: Univariate analysis showed: 1) TNF-238*A allele was associated with severe osteolysis (odds ratio, OR = 6.59, p = 0.005, population attributable risk, PAR 5.2%); 2) carriers of the IL6-174*G allele were 2.5 times more prone to develop severe osteolysis than non-carriers (OR = 2.51, p = 0.007, PAR = 31.5%); 3) the carriage of IL2-330*G allele was associated with protection from severe osteolysis (OR = 0.55, p = 0.043). Based on logistic regression, the alleles TNF-238*A and IL6-174*G were independent predictors for the development of severe acetabular osteolysis. Carriers of TNF-238*A had increased cumulative hazard of THA failure according to Cox model (p = 0.024). In contrast, IL2-330*G allele predicted lower cumulative hazard of THA failure (p = 0.019). CONCLUSION: Genetic variants of proinflammatory cytokines TNF-alpha and IL-6 confer susceptibility to severe OL. In this way, presence of the minor TNF allele could increase the cumulative risk of THA failure. Conversely, SNP in the IL2 gene may protect carriers from the above THA complications.
- MeSH
- alely MeSH
- cytokiny genetika MeSH
- dospělí MeSH
- genetické asociační studie MeSH
- interleukin-2 genetika MeSH
- interleukin-6 genetika MeSH
- jednonukleotidový polymorfismus MeSH
- lidé středního věku MeSH
- lidé MeSH
- náhrada kyčelního kloubu škodlivé účinky MeSH
- odds ratio MeSH
- osteolýza etiologie genetika MeSH
- proporcionální rizikové modely MeSH
- receptory cytokinové genetika MeSH
- rizikové faktory MeSH
- selhání protézy MeSH
- senioři MeSH
- stupeň závažnosti nemoci MeSH
- TNF-alfa genetika MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- práce podpořená grantem MeSH
- srovnávací studie MeSH
- MeSH
- diagnostické techniky molekulární využití MeSH
- endoteliální buňky imunologie patologie MeSH
- farmakogenetika metody trendy MeSH
- genom bakteriální genetika imunologie MeSH
- infekční nemoci etiologie genetika imunologie MeSH
- lidé MeSH
- polymorfismus genetický genetika imunologie MeSH
- přehledová literatura jako téma MeSH
- přirozená imunita fyziologie genetika imunologie MeSH
- prognóza MeSH
- projekt Lidský genom dějiny organizace a řízení MeSH
- receptory cytokinové genetika imunologie MeSH
- sepse etiologie genetika imunologie MeSH
- zánět etiologie genetika imunologie MeSH
- Check Tag
- lidé MeSH
- MeSH
- antigen Ki-1 genetika izolace a purifikace MeSH
- exprese genu genetika imunologie MeSH
- finanční podpora výzkumu jako téma MeSH
- financování organizované MeSH
- genetické markery genetika imunologie MeSH
- lidé MeSH
- lymfoproliferativní nemoci diagnóza genetika krev MeSH
- polymerázová řetězová reakce využití MeSH
- receptory cytokinové genetika imunologie MeSH
- reziduální nádor MeSH
- Check Tag
- lidé MeSH
Cytokine gene polymorphisms (CGP) have been implicated in the pathogenesis of immune-mediated diseases including transplant complications via their effect on cytokine production and regulation. This study aimed to determine population frequencies of selected cytokine single nucleotide polymorphisms in the healthy Czech population and compare them with the data from other selected European populations. CGP were genotyped by polymerase chain reaction with sequence-specific primers (PCR-SSP) using the Heidelberg kit in 120 unrelated Czech healthy individuals. Chi-squared analysis was used to test for a deviation from Hardy-Weinberg equilibrium. Allelic and genotype frequencies and carriage rates were determined for 22 CGP located within 13 cytokine genes in total. The frequencies observed in this study were similar to those available from the other two geographically close Central European centres, but they differed for several CGP from the data reported in south European populations. The data on the distribution of 22 CGP in the healthy Czech population reported here may be utilized to investigate possible associations of CGP with diseases or transplantation outcome.
- MeSH
- běloši MeSH
- cytokiny genetika imunologie MeSH
- dospělí MeSH
- financování organizované MeSH
- frekvence genu MeSH
- jednonukleotidový polymorfismus MeSH
- lidé středního věku MeSH
- lidé MeSH
- receptory cytokinové genetika imunologie MeSH
- senioři MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Geografické názvy
- Česká republika MeSH
- Evropa MeSH
- MeSH
- Crohnova nemoc etiologie genetika mikrobiologie MeSH
- cytokiny analýza MeSH
- lidé MeSH
- polymorfismus genetický MeSH
- receptory cytokinové genetika MeSH
- ulcerózní kolitida etiologie genetika mikrobiologie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- kongresy MeSH
