Východiska: Dříve provedené studie hodnotily souvislost polymorfizmu IL-8 -251T>A a IL-18 -607C>A s rizikem karcinomu prsu v různých populacích, ale výsledky zůstávají nekonzistentní a neprůkazné. Provedli jsme tedy tuto metaanalýzu s cílem prozkoumat souvislosti. Metody: Komplexní vyhledávání literatury v databázích PubMed, EMBASE, Web of Science, Scopus, SciELO, SID, and CNKI z hlediska všech vhodných studií publikovaných do 1. října 2020. Pro hodnocení intenzity souvislosti byly použity souhrnné poměry šancí (odds ratio – OR) s 95% intervaly spolehlivosti (confidence interval – CI). Výsledky: Bylo vybráno celkem 12 studií případů a kontrol o polymorfizmu IL-8 -251T>A vč. 7 studií s 2 370 případy a 2 314 kontrolami a 5 studií o polymorfizmu IL-18 -607C>A s 900 případy a 882 kontrolami. Souhrnná data ukázala, že polymorfizmy IL-8 -251T>A (AT vs. TT: OR = 1,187; 95% CI 1,038–1,356; p = 0,012) a IL-18 -607C>A (A vs. T: OR = 1,205; 95% CI 1,055–1,377; p = 0,006; AA vs. TT: OR = 1,379; 95% CI 1,056–1,802; p = 0,018; a AA vs. AT+TT: OR = 1,329; 95% CI 1,053–1,678; p = 0,017) měly obecně souvislost se zvýšeným rizikem karcinomu prsu. Navíc když byly studie stratifikovány podle etnik, u IL-8 -251T>A byla významná souvislost s rizikem karcinomu prsu u Afričanek. Testy publikačního zkreslení u metaanalýzy žádné publikační zkreslení neprokázaly. Závěr: Tato metaanalýza odhalila, že polymorfizmus IL-8 -251T>A a IL-18 -607C>A je spojen s náchylností ke karcinomu prsu. Pro lepší vyhodnocení těchto asociací je ovšem třeba dalších multicentrických studií s různými etniky.
Background: Previous studies have evaluated the association of IL-8 -251T>A and IL-18 -607C>A polymorphisms with a risk of breast cancer in different populations, but the results remain inconsistent and inconclusive. Thus, we performed this meta-analysis to explore the associations. Methods: A comprehensive literature search in PubMed, EMBASE, Web of Science, Scopus, SciELO, SID, and CNKI for all eligible studies published up to October 1, 2020. The pooled odds ratios (ORs) with 95% confidence intervals (CIs) were used to evaluate the intensity of associations. Results: A total of 12 case-control studies including seven studies with 2,370 cases and 2,314 controls on IL-8 -251T>A, and five studies with 900 cases and 882 controls on IL-18 -607C>A polymorphism were selected. Pooled data showed that IL-8 -251T>A (AT vs. TT: OR= 1.187; 95% CI 1.038–1.356; P = 0.012) and IL-18 -607C>A polymorphisms (A vs. T: OR = 1.205; 95% CI 1.055–1.377; P = 0.006; AA vs. TT: OR = 1.379; 95% CI 1.056–1.802; P = 018; and AA vs. AT+TT: OR = 1.329; 95% CI 1.053–1.678; P = 0.017) were associated with increased risk of breast cancer in overall. Moreover, when the studies were stratified by ethnicity, the IL-8 -251T>A was significantly associated with breast cancer risk in Africans. Publication bias tests provide no evidence of presence of publication bias in a meta-analysis. Conclusion: This meta-analysis results revealed that the IL-8 -251T>A and IL-18 -607C>A polymorphisms are associated with susceptibility to breast cancer. However, further multicenter studies with larger sample sizes in different ethnicities are required to make a better assessment of these associations.
Host genetic predispositions to dysregulated immune response can influence the development of the aggressive form of periodontitis (AgP) through susceptibility to oral dysbiosis and subsequent host-microbe interaction. This case-control study aimed to perform a multilocus analysis of functional variants in selected interleukin (IL) genes in patients with the generalized form of AgP in a homogenous population. Twelve polymorphisms in IL-1 gene cluster, IL-6 and its receptor, IL-10, IL-17A, and IL-18 were determined in 91 AgP patients and 210 controls. Analysis of seven selected periodontal bacteria in subgingival sulci/pockets was performed with a commercial DNA-microarray kit in a subgroup of 76 individuals. The pilot in vitro study included stimulation of peripheral blood monocytes (PBMC) from 20 individuals with periodontal bacteria and measurement of IL-10 levels using the Luminex method. Only the unctional polymorphism IL‑10-1087 A/G (rs1800896) and specific IL-10 haplotypes were associated with the development of the disease (P < 0.05, Pcorr > 0.05). Four bacterial species occurred more frequently in AgP than in controls (P < 0.01, Pcorr < 0.05). Elevated IL-10 levels were found in AgP patients, carriers of IL‑10-1087GG genotype, and PBMCs stimulated by periodontal bacteria (P < 0.05, Pcorr > 0.05). We therefore conclude that a combination of genetic predisposition to the altered expression of IL-10 and the presence of specific periodontal bacteria may contribute to Th1/Th2 balance disruption and AgP development.
- MeSH
- agresivní parodontitida genetika imunologie mikrobiologie MeSH
- alely MeSH
- Bacteria genetika MeSH
- dospělí MeSH
- frekvence genu genetika MeSH
- genetická predispozice k nemoci genetika MeSH
- genotyp MeSH
- haplotypy genetika MeSH
- interleukin-1 genetika MeSH
- interleukin-10 genetika MeSH
- interleukin-17 genetika MeSH
- interleukin-18 genetika MeSH
- interleukin-6 genetika MeSH
- interleukiny genetika metabolismus MeSH
- jednonukleotidový polymorfismus genetika MeSH
- lidé MeSH
- parodontitida genetika imunologie MeSH
- studie případů a kontrol MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- Geografické názvy
- Česká republika MeSH
Coronary artery disease (CAD) is a clinical manifestation of atherosclerosis in the arteries supplying myocardium. Inflammation is the cornerstone in the development and progression of atherosclerosis. Amongst the various biomolecules tumour necrosis factor-α (TNF-α), interleukin-18 (IL-18) and interleukin-1β (IL-1β) build an inflammatory bionetwork in developing the disease. In this study we investigated the association of TNF-α SNPs [–308G/A (rs1800629), −1031T/C (rs1799964), −863C/A (rs1800630)]; IL-18 [–137G/C (rs187238)] and IL-1β SNPs [+3954C/T (rs1143634), −31C/T (rs1143627), and −511C/T (rs16944)] with coronary artery disease risk in Kashmiri population. A total of 200 cases and 260 controls were recruited in the study. Logistic regression analysis was done to investigate the association between SNPs and CAD risk. In case of TNF-α, the −308G/A-A/A and −863A/A showed an association with disease while −1031T/C was found to have an inverse relation. The IL-18–137G/C showed no statistically significant difference between controls and cases. For IL-1β the +3954C/T and −31C/T SNP variants showed no disease association while −511T/T showed significant association. Haplotypic analysis revealed the haplotype ATCGCC and GTACCTC to be associated with CAD risk and GTCGTTT, in particular, showing a profound association. Overall, our study suggests that TNF-α and IL-1β promoter polymorphisms may act as genetic risk factors in developing the coronary artery disease.
- MeSH
- ateroskleróza genetika patofyziologie MeSH
- biologické markery MeSH
- interleukin-18 genetika imunologie MeSH
- interleukin-1beta genetika imunologie MeSH
- koronární nemoc genetika MeSH
- lidé MeSH
- polymorfismus genetický MeSH
- studie případů a kontrol MeSH
- TNF-alfa genetika imunologie MeSH
- zánět * krev patofyziologie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- práce podpořená grantem MeSH
Tick saliva contains a number of effector molecules that inhibit host immunity and facilitate pathogen transmission. How tick proteins regulate immune signaling, however, is incompletely understood. Here, we describe that loop 2 of sialostatin L2, an anti-inflammatory tick protein, binds to annexin A2 and impairs the formation of the NLRC4 inflammasome during infection with the rickettsial agent Anaplasma phagocytophilum Macrophages deficient in annexin A2 secreted significantly smaller amounts of interleukin-1β (IL-1β) and IL-18 and had a defect in NLRC4 inflammasome oligomerization and caspase-1 activation. Accordingly, Annexin a2-deficient mice were more susceptible to A. phagocytophilum infection and showed splenomegaly, thrombocytopenia, and monocytopenia. Providing translational support to our findings, better binding of annexin A2 to sialostatin L2 in sera from 21 out of 23 infected patients than in sera from control individuals was also demonstrated. Overall, we establish a unique mode of inflammasome evasion by a pathogen, centered on a blood-feeding arthropod.
- MeSH
- Anaplasma phagocytophilum genetika imunologie MeSH
- annexin A2 chemie genetika imunologie MeSH
- arachnida jako vektory chemie genetika imunologie MeSH
- cystatiny chemie genetika imunologie MeSH
- ehrlichióza imunologie mikrobiologie patologie MeSH
- Escherichia coli genetika metabolismus MeSH
- imunitní únik * MeSH
- inflamasomy genetika imunologie MeSH
- interleukin-18 genetika imunologie MeSH
- interleukin-1beta genetika imunologie MeSH
- kaspasa 1 genetika imunologie MeSH
- kaspasy genetika imunologie MeSH
- klíště chemie genetika imunologie MeSH
- lidé MeSH
- makrofágy imunologie mikrobiologie MeSH
- molekulární modely MeSH
- myši MeSH
- protein - isoformy chemie genetika imunologie MeSH
- proteiny regulující apoptózu chemie genetika imunologie MeSH
- proteiny vázající vápník chemie genetika imunologie MeSH
- regulace genové exprese MeSH
- rekombinantní proteiny chemie genetika imunologie MeSH
- sekvence aminokyselin MeSH
- signální transdukce MeSH
- vazba proteinů MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
Low-grade inflammation links obesity, insulin resistance, and cardiovascular diseases. We investigated the effects of laparoscopic sleeve gastrectomy (LSG) on expression profile of genes involved in inflammatory pathways in subcutaneous adipose tissue (SCAT) and peripheral monocytes (PM). At baseline, obese group had significantly increased mRNA expression of proinflammatory chemokines (CCL-3, -17, -22), chemokine receptor CCR1 and cytokines (IL-10, IL-18) in SCAT and chemokine and other proinflammatory receptors (CCR-1, -2, -3, TLR-2, -4) in PM relative to control group. LSG decreased body weight, improved metabolic profile and reduced mRNA expression of up-regulated chemokine receptors, chemokines and cytokines in SCAT. In contrast, expression profiles in PM were largely unaffected by LSG. We conclude that LSG improved proinflammatory profile in subcutaneous fat but not in peripheral monocytes. The sustained proinflammatory and chemotactic profile in PM even 2 years after LSG may contribute to partial persistence of metabolic complications in obese patients after metabolic surgery.
- MeSH
- chemokiny CC genetika metabolismus MeSH
- dospělí MeSH
- exprese genu * MeSH
- gastrektomie metody MeSH
- hmotnostní úbytek MeSH
- interleukin-10 genetika metabolismus MeSH
- interleukin-18 genetika metabolismus MeSH
- laparoskopie MeSH
- lidé středního věku MeSH
- lidé MeSH
- messenger RNA genetika metabolismus MeSH
- monocyty metabolismus patologie MeSH
- obezita genetika metabolismus patologie chirurgie MeSH
- orgánová specificita MeSH
- podkožní tuk metabolismus patologie MeSH
- receptory CCR genetika metabolismus MeSH
- stanovení celkové genové exprese MeSH
- toll-like receptor 2 genetika metabolismus MeSH
- toll-like receptor 4 genetika metabolismus MeSH
- zánět genetika metabolismus patologie chirurgie MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
It is known that interleukin-18 (IL-18) is a proinflammatory cytokine with dual effects on tumor development and progression. It can increase the immune defense against tumor cells. Polymorphisms in the IL-18 genes are known to influence both expression levels and may be associated with outcome of cancers. This study was aimed to find out the possible association of IL-18 polymorphism at position –607 C/A (rs1946518) with breast cancer in a sample of Iranian population. We investigated IL-18 rs1946518 polymorphism on 72 breast cancer patients and 93 cancer free women. Genotyping was done using amplification refractory mutation system-PCR (ARMS-PCR). We found no significant differences between breast cancer patients and control subjects regarding IL-18 rs1946518 polymorphism (χ2=1.78, p=0.411). In conclusion, our finding showed that IL-18 rs1946518 polymorphism was not associated with breast cancer in a sample of Iranian population.
- MeSH
- dospělí MeSH
- genetická predispozice k nemoci MeSH
- interleukin-18 genetika MeSH
- jednonukleotidový polymorfismus MeSH
- lidé středního věku MeSH
- lidé MeSH
- nádory prsu genetika MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- ženské pohlaví MeSH
- Publikační typ
- práce podpořená grantem MeSH
- Geografické názvy
- Írán MeSH
Mycobacterium avium subsp. avium (MAA) and Mycobacterium avium subsp. hominissuis (MAH) are the most common mycobacterial species isolated from granulomatous lesions in swine in countries with controlled bovine tuberculosis. This study is focused on the immunological aspect of MAA and MAH infection in pigs. We detected induction of humoral and cell-mediated immunity in experimentally infected pigs. Specific antibodies were analyzed in serum by ELISA and the IFN-γ release assay was used for evaluation of cell-mediated immunity. While MAA induced a significant increase of both types of immune responses, MAH-infected pigs had an unvarying level of specific antibodies and showed low cell-mediated immunity with high individual variability. The subsequent in vitro experiment confirmed the lower immunogenicity of the MAH strain in comparison to MAA. MAH-infected porcine monocyte-derived macrophages showed a weaker induction of pro-inflammatory mediators in comparison to MAA, which included mRNA for IL-1β, TNF-α, IL-23p19, IL-18 and chemokines CCL-3, CCL-5, CXCL-8 and CXCL-10. Additionally, qualitative proteomic analysis revealed 28 proteins exclusively in MAA and 7 proteins unique to MAH. In conclusion, closely related M. avium subspecies MAA and MAH showed different capacities to stimulate the porcine immune system. From a diagnostic point of view, the IFN-γ release assay showed higher sensitivity than the detection of specific antibodies by ELISA and seems to be an effective tool for discrimination of MAA-infected pigs. In the case of MAH infection, the IFN-γ release assay could fail because of the low immunogenic capacity of the MAH strain.
- MeSH
- buněčná imunita MeSH
- interleukin-18 genetika imunologie metabolismus MeSH
- interleukin-23 - podjednotka p19 genetika imunologie MeSH
- makrofágy imunologie MeSH
- mediátory zánětu imunologie MeSH
- Mycobacterium avium klasifikace izolace a purifikace fyziologie MeSH
- nemoci prasat genetika imunologie mikrobiologie MeSH
- prasata MeSH
- TNF-alfa genetika imunologie MeSH
- tuberkulóza imunologie veterinární MeSH
- zvířata MeSH
- Check Tag
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
One of the promising approaches in the therapy of ulcerative colitis is administration of butyrate, an energy source for colonocytes, into the lumen of the colon. This study investigates the effect of butyrate producing bacterium Clostridium tyrobutyricum on dextran sodium sulphate (DSS)-induced colitis in mice. Immunocompetent BALB/c and immunodeficient severe combined immunodeficiency (SCID) mice reared in specific-pathogen-free (SPF) conditions were treated intrarectally with C. tyrobutyricum 1 week prior to the induction of DSS colitis and during oral DSS treatment. Administration of DSS without C. tyrobutyricum treatment led to an appearance of clinical symptoms - bleeding, rectal prolapses and colitis-induced increase in the antigen CD11b, a marker of infiltrating inflammatory cells in the lamina propria. The severity of colitis was similar in BALB/c and SCID mice as judged by the histological damage score and colon shortening after 7 days of DSS treatment. Both strains of mice also showed a similar reduction in tight junction (TJ) protein zonula occludens (ZO)-1 expression and of MUC-2 mucin depression. Highly elevated levels of cytokine tumour necrosis factor (TNF)-α in the colon of SCID mice and of interleukin (IL)-18 in BALB/c mice were observed. Intrarectal administration of C. tyrobutyricum prevented appearance of clinical symptoms of DSS-colitis, restored normal MUC-2 production, unaltered expression of TJ protein ZO-1 and decreased levels of TNF-α and IL-18 in the descending colon of SCID and BALB/c mice, respectively. Some of these features can be ascribed to the increased production of butyrate in the lumen of the colon and its role in protection of barrier functions and regulation of IL-18 expression.
- MeSH
- akutní nemoc MeSH
- antigeny CD11b biosyntéza genetika MeSH
- aplikace rektální MeSH
- bakteriální translokace MeSH
- butyráty metabolismus MeSH
- Clostridium tyrobutyricum fyziologie MeSH
- fosfoproteiny biosyntéza genetika MeSH
- imunokompetence MeSH
- interleukin-18 biosyntéza genetika MeSH
- kolon metabolismus mikrobiologie patologie MeSH
- mastné kyseliny metabolismus MeSH
- membránové proteiny biosyntéza genetika MeSH
- mucin 2 biosyntéza genetika MeSH
- muciny biosyntéza MeSH
- myši inbrední BALB C MeSH
- myši SCID MeSH
- myši MeSH
- organismy bez specifických patogenů MeSH
- probiotika terapeutické užití MeSH
- síran dextranu toxicita MeSH
- těžká kombinovaná imunodeficience genetika imunologie MeSH
- TNF-alfa biosyntéza genetika MeSH
- ulcerózní kolitida chemicky indukované genetika imunologie mikrobiologie patologie MeSH
- zvířata MeSH
- Check Tag
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
BACKGROUND: Our study focused on the ability of epicardial adipocytes to produce bioactive substances and compare the extent of this production with the production of adipokines in visceral adipocytes, which are well known endocrine cells capable of contributing to the development of atherosclerosis. MATERIAL AND METHODS: The gene expression of human cytokines (IL-6, IL-8, IL-18, RANTES and MCP-1) and adipokines (leptin and adiponectin) was measured in primary cell lines of epicardial and visceral adipocytes, both in undifferentiated and mature statuses, after a 21-day-long differentiation protocol. Each condition was assayed in triplicate in two independent primary cell lines obtained from two different donors. RESULTS: The epicardial preadipocytes showed an increased expression of IL-8 (3.25-fold, p<0.05) compared with visceral preadipocytes. The expression of the atheroprotective adiponectin in epicardial preadipocytes was minimal compared with the expression in visceral preadipocytes (p<0.0001). Moreover, the expression of the genes of interest was dependent on the differentiation degree and cell origin. We observed an altered expression of the proinflammatory genes IL-8 (0.016-fold, p<0.01) and MCP-1 (0.19-fold, p<0.05) in differentiated epicardial adipocytes compared with undifferentiated adipocytes. The epicardial adipocytes showed an increased expression of IL-6 (8.13-fold, p<0.05) compared with the visceral adipocytes. CONCLUSION: Our results suggest that epicardial adipocytes substantially differ from visceral adipocytes and might locally contribute to the pathogenesis of coronary atherosclerosis.
- MeSH
- buněčná diferenciace fyziologie MeSH
- chemokin CCL2 genetika MeSH
- chemokin CCL5 genetika MeSH
- cytokiny genetika MeSH
- dospělí MeSH
- exprese genu fyziologie MeSH
- interleukin-18 genetika MeSH
- interleukin-6 genetika MeSH
- interleukin-8 genetika MeSH
- kultivované buňky MeSH
- lidé MeSH
- nitrobřišní tuk cytologie fyziologie MeSH
- perikard cytologie fyziologie MeSH
- pilotní projekty MeSH
- tukové buňky cytologie fyziologie MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- srovnávací studie MeSH
Interleukin-18 (IL-18) plays a critical role in immune response, contributing to the pathogenesis and pathophysiology of infectious diseases. Polymorphisms in the IL-18 genes are known to influence expression levels and may be associated with outcome of infections. The objective of this study was to determine whether the presence of IL-18 polymorphisms –607 A/C (rs1946518) was associated with tuberculosis disease. We investigated the functional polymorphism of IL-18 (rs1946518) in 174 patients with pulmonary tuberculosis (PTB) and 177 healthy subjects. Genotype analysis was done using tetra amplification refractory mutation system-PCR (T-ARMS-PCR). The allelic and genotypic frequencies of the IL-18 polymorphism did not differ significantly between PTB and the controls. Our finding suggests that IL-18 polymorphism (rs1946518) may not be a risk factor for susceptibility to tuberculosis in a sample of Iranian population. Further studies are required to validate our findings.
- MeSH
- frekvence genu MeSH
- genetická predispozice k nemoci MeSH
- genotyp MeSH
- interleukin-18 genetika MeSH
- jednonukleotidový polymorfismus MeSH
- lidé středního věku MeSH
- lidé MeSH
- plicní tuberkulóza genetika MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Geografické názvy
- Írán MeSH