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
Fusarium-derived mycotoxin deoxynivalenol (DON) usually induces diarrhea, vomiting and gastrointestinal inflammation. We studied the cytotoxic effect of DON on porcine small intestinal epithelium using the intestinal porcine epithelial cell line IPEC-J2. We screened out differentially expressed genes (DEGs) using RNA-seq and identified 320 upregulated genes and 160 downregulated genes. The enrichment pathways of these DEGs focused on immune-related pathways. DON induced proinflammatory gene expression, including cytokines, chemokines and other inflammation-related genes. DON increased IL1A, IL6 and TNF-α release and DON activated the phosphorylation of extracellular signal-regulated kinase-1 and-2 (ERK1/2), JUN N-terminal kinase (JNK) and p38 MAPK. A p38 inhibitor attenuated DON-induced IL6, TNF-α, CXCL2, CXCL8, IL12A, IL1A, CCL20, CCL4 and IL15 production, while an ERK1/2 inhibitor had only a small inhibitory effect on IL15 and IL6. An inhibitor of p38 MAPK decreased the release of IL1A, IL6 and TNF-α and an inhibitor of ERK1/2 partly attenuated protein levels of IL6. These data demonstrate that DON induces proinflammatory factor production in IPEC-J2 cells by activating p38 and ERK1/2.
- MeSH
- buněčné linie MeSH
- epitelové buňky účinky léků imunologie metabolismus MeSH
- interleukin-1 genetika MeSH
- interleukin-6 genetika MeSH
- MAP kinasový signální systém účinky léků genetika imunologie MeSH
- mitogenem aktivované proteinkinasy p38 metabolismus MeSH
- prasata MeSH
- střevní sliznice účinky léků imunologie metabolismus MeSH
- TNF-alfa genetika MeSH
- transkriptom účinky léků MeSH
- trichotheceny toxicita MeSH
- viabilita buněk účinky léků MeSH
- zánět MeSH
- zvířata MeSH
- Check Tag
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Overactivation of the innate immune system together with the impaired downstream pathway of type I interferon-responding genes is a hallmark of rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), and systemic sclerosis (SSc). To date, limited data on the cross-disease innate gene signature exists among those diseases. We compared therefore an innate gene signature of Toll-like receptors (TLRs), seven key members of the interleukin (IL)1/IL1R family, and CXCL8/IL8 in peripheral blood mononuclear cells from well-defined patients with active stages of RA (n = 36, DAS28 ≥ 3.2), SLE (n = 28, SLEDAI > 6), and SSc (n = 22, revised EUSTAR index > 2.25). Emerging diversity and abundance of the innate signature in RA patients were detected: RA was characterized by the upregulation of TLR3, TLR5, IL1RAP/IL1R3, IL18R1, and SIGIRR/IL1R8 when compared to SSc (Pcorr < 0.02) and of TLR2, TLR5, and SIGIRR/IL1R8 when compared to SLE (Pcorr < 0.02). Applying the association rule analysis, six rules (combinations and expression of genes describing disease) were identified for RA (most frequently included high TLR3 and/or IL1RAP/IL1R3) and three rules for SLE (low IL1RN and IL18R1) and SSc (low TLR5 and IL18R1). This first cross-disease study identified emerging heterogeneity in the innate signature of RA patients with many upregulated innate genes compared to that of SLE and SSc.
- MeSH
- dospělí MeSH
- interleukin-1 genetika metabolismus MeSH
- interleukin-8 genetika metabolismus MeSH
- leukocyty mononukleární metabolismus MeSH
- lidé středního věku MeSH
- lidé MeSH
- přirozená imunita genetika MeSH
- receptory interleukinu-1 - typ I genetika metabolismus MeSH
- revmatoidní artritida krev genetika imunologie MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- systémová sklerodermie krev genetika imunologie MeSH
- systémový lupus erythematodes krev genetika imunologie MeSH
- toll-like receptory genetika metabolismus MeSH
- transkriptom 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
- časopisecké články MeSH
The occurrence and development of lung cancer is closely related to inflammation. Thus, we conducted the present study to investigate the effects of IL-37 (Interleukin 37), a newly identified anti-inflammatory factor, on non-small cell lung cancer (NSCLC), which accounts for about 85% of all lung cancers. To address the function of IL-37 in NSCLC, we first evaluated IL-37 expression in the human NSCLC tissues; then the IL-37 function was assessed in vitro and in vivo in a xenografted lung tumor model. IL-37 was barely expressed in the NSCLC tissue but highly expressed in the adjacent normal tissue. This expression profile was validated by ELISA (Enzyme-linked immunoassay), western blot and immunohistochemical staining. Recombinant IL-37 could suppress cell migration, invasion and proliferation and promote cell apoptosis in NSCLC cell line A549 and SK-MES-1. IL-37 inhibited the IL-6/STAT3 pathway and also the downstream targets Bcl-2, NEDD9 and Cyclin D1. Overexpressing IL-6 or constitutive active STAT3 eliminated the anti-tumor effects of IL-37. Furthermore, IL-37 expression in vivo could inhibit the cancer development. Our results showed that IL-37 plays an inhibitory role in lung cancer development, possibly through IL-6/STAT3 pathway.
- MeSH
- interleukin-1 genetika metabolismus MeSH
- lidé MeSH
- mediátory zánětu metabolismus MeSH
- nádorová transformace buněk imunologie MeSH
- nemalobuněčný karcinom plic * genetika metabolismus patologie MeSH
- receptory interleukinu-6 antagonisté a inhibitory genetika metabolismus MeSH
- signální transdukce MeSH
- transkripční faktor STAT3 antagonisté a inhibitory genetika metabolismus MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- práce podpořená grantem MeSH
Interleukin 1 (IL-1) family is a group of cytokines with multiple local and systemic effects, which regulates both innate and adaptive immune responses. Generally, most IL-1 family cytokines express prevailing pro-inflammatory activities (IL-1α, IL-1β, IL-18, IL-33, IL-36 α, β, γ), whereas others are anti-inflammatory (IL-1Ra (IL-1 receptor antagonist), IL-36Ra, IL-38, IL-37). In addition to their immunomodulatory roles, some of them are also involved in the physiological modulation of homeostatic processes and directly affect mRNA transcription. IL-1 family cytokines bind to specific receptors composed of a ligand-binding chain and an accessory chain. The pro-inflammatory effects of IL-1 family cytokines are regulated on the level of transcription, enzymatic processing of precursors, release of soluble antagonists, and expression of decoy receptors. Members of the IL-1 family regulate the recruitment and activation of effector cells involved in innate and adaptive immunity, but they are also involved in the pathogenesis of chronic disorders, including inflammatory bowel disease, rheumatoid arthritis, and various autoimmune and autoinflammatory diseases. There are only limited data regarding the role of IL-1 cytokines in transplantation. In recent years, targeted therapeutics affecting IL-1 have been used in multiple clinical studies. In addition to the recombinant IL-1Ra, anakinra (highly effective in autoinflammatory diseases and tested for other chronic diseases), the monoclonal antibodies canakinumab, gevokizumab, and rilonacept (a long-acting IL-1 receptor fusion protein) provide further options to block IL-1 activity. Furthermore, new inhibitors of IL-18 (GSK 1070806, ABT-325, rIL-18BP (IL-18 binding protein)) and IL-33 (CNTO-7160) are presently under clinical studies and other molecules are being developed to target IL-1 family cytokines.
- MeSH
- interleukin-1 genetika imunologie MeSH
- lidé MeSH
- multigenová rodina * MeSH
- transplantace orgánů MeSH
- transplantační imunologie * MeSH
- zánět genetika imunologie MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
BACKGROUND: Recurrent aphthous stomatitis (RAS) is one of the most common oral chronic ulcerative disease in which proinflammatory cytokines such as interleukin-1 (IL-1) and interleukin-6 (IL-6) are thought to play an important role. The aim of this study was to investigate the possible association between polymorphisms in the IL-1 cytokine family, IL-6 or its receptor and RAS in the Czech population. METHODS: A total of 248 subjects, 184 healthy controls, and 64 patients with RAS were genotyped for IL-1A-889C>T, IL-1B-511C>T, IL-1B+3953C>T, IL-1RN86 bp variable number of tandem repeats (VNTRs) in intron 2, IL-6-597G>A, IL-6-572G>C, IL-6-174G>C, and IL-6R+48992A>C by polymerase chain reaction (PCR) methods. RESULTS: No significant differences between investigated polymorphisms in healthy subjects and patients with RAS were detected (P>.05). In addition, complex analysis also revealed similar IL-1 or IL-6 haplotype frequencies between both groups (P>.05). CONCLUSIONS: In conclusion, IL-1 and IL-6 or its receptor gene variants cannot be used as markers for identification of Czech patients with increased risk of recurrent aphthous stomatitis.
- MeSH
- aftózní stomatitida genetika MeSH
- dospělí MeSH
- genetické asociační studie MeSH
- interleukin-1 genetika MeSH
- interleukin-6 genetika MeSH
- jednonukleotidový polymorfismus * MeSH
- lidé středního věku MeSH
- lidé MeSH
- recidiva MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
Úvod a cíl studie: Genetické predispozice hrají významnou roli v etiopatogenezi jak chronické parodontitidy (CP), tak i diabetes mellitus (DM), mezi kterými existuje reciproční vztah. U obou chorob jsou za kandidátní považovány geny pro imunoregulační faktory, k nimž se řadí signální peptidy zvané cytokiny. Cílem naší studie bylo analyzovat polymorfismy ve vybraných cytokinech, konkrétně v interleukin-1 (IL-1) genovém klasteru a v IL-6 genu, u pacientů s CP s/bez DM a porovnat je se zdravou populací. Metodika: Do studie případů a kontrol (tzv. case-control study) jsme zařadili celkem 590 osob: 226 zdravých; 248 pacientů pouze s CP, 36 pacientů s CP i DM 1. typu (T1DM), 80 pacientů s CP a DM 2. typu (T2DM). Pro genotypizaci jsme využili postupů založených na polymerázové řetězové reakci (PCR) a následné restrikční analýze. Výsledky: Frekvence alel a genotypů sledovaných polymorfismů ve vybraných cytokinech, kromě varianty v IL-1B genu se mezi skupinami pacientů a zdravými jedinci statisticky významně nelišily. V IL-1 genovém klastru jsme však nalezli protektivní haplotyp u CP a haplotypy zvyšující riziko rozvoje CP u pacientů s T2DM i s T1DM. Rovněž v genu pro IL-6 jsme prokázali signifikantní rozdíl ve frekvenci haplotypu GGG mezi pacienty s CP a zdravými jedinci. Závěr: Naše výsledky naznačují, že na rozdíl od analýz jednotlivých polymorfismů různé haplotypy v IL-1 genovém klasteru i v promotoru genu pro IL-6 mohou ovlivňovat riziko rozvoje CP u pacientů s/bez DM v české populaci. Domníváme se, že stanovení haplotypů má, oproti sledování jednotlivých alelických a genotypových frekvencí, lepší výpovědní hodnotu a měla by mu být dána při genetické analýze komplexních nemocí přednost.
Introduction and aim of study: Genetic predispositions play an important role in the etiopathogenesis of periodontal diseases (CP) and diabetes mellitus (DM). Recent studies have also proven a bidirectional interrelationship between these conditions. The immunoregulatory factors, including signal peptides, so called cytokines, are considered as candidate genes for both of these diseases. The aim of our study was to analyse polymorphisms in selected cytokines, namely in the interleukin-1 (IL-1) gene cluster and IL-6 gene, in patients with CP and with/without DM and compare them with the healthy population. Methods: 590 subjects were enrolled in this case-control study: 226 healthy/non-periodontitis subjects, 248 patients only with CP, 36 patients with CP and type 1 DM (T1DM), 80 patients with CP and type 2 DM (T2DM). For genotyping methods based on polymerase chain reaction (PCR) and subsequent restriction analysis were used. Results: The allele and genotype frequencies of the studied polymorphisms, except for a variant in the IL-1B gene, did not differ significantly between the groups of patients and healthy controls. However, in the IL-1 gene cluster, a protective haplotype in CP and risk haplotypes for CP in patients with T2DM or with T1DM were found. In addition, in the IL-6 gene, a significant difference in GGG haplotype frequencies between the groups of patients with CP and healthy controls was identified. Conclusion: Our results suggest, that contrary to analyses of individual polymorphisms, different haplotypes in the IL-1 gene cluster and IL-6 gene promoter may affect the risk for CP development in patients with/without DM in Czech population. We assume that the determination of haplotypes may have a better predictive value than study of individual allele and genotype frequencies and it should be preferred in genetic analysis of complex diseases.
- MeSH
- chronická nemoc MeSH
- cytokiny MeSH
- diabetes mellitus 1. typu genetika imunologie metabolismus MeSH
- diabetes mellitus 2. typu genetika imunologie metabolismus MeSH
- dospělí MeSH
- frekvence genu MeSH
- genetická predispozice k nemoci * MeSH
- genotypizační techniky MeSH
- haplotypy MeSH
- interleukin-1 fyziologie genetika MeSH
- interleukin-6 fyziologie genetika MeSH
- komplikace diabetu * MeSH
- lidé středního věku MeSH
- lidé MeSH
- parodontitida * genetika imunologie MeSH
- polymorfismus genetický genetika MeSH
- senioři MeSH
- statistika jako téma MeSH
- studie případů a kontrol MeSH
- ztráta parodontálního úponu diagnóza 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
Alergická rýma a alergie jsou stavy, na jejichž patogenezi se podílejí genetické faktory i faktory vnějšího prostředí. Uplatnění běžných jednonukleotidových polymorfismů v celogenomových asociačních studiích (GWAS) urychlilo hledání nových genů a také potvrdilo úlohu některých již dříve popsaných genů, které by se mohly podílet na vzniku alergické rýmy a alergie. Cílem tohoto přehledového článku je poskytnout přehled o genetickém základu alergické rýmy a souvisejících alergických fenotypů se zaměřením na GWAS. Nové poznatky: Během posledního desetiletí bylo publikováno více než 20 GWAS týkajících se alergické rýmy a souvisejících fenotypů. Ukázalo se, že alergická onemocnění a znaky jsou podmíněné velkým počtem genetických lokusů, z nichž se pro více než dva alergické fenotypy zdají být důležitými IL33/IL1RL1, IL‑13‑RAD50 a C11orf30/LRRC32. GWAS dále odrážejí genetickou heterogenitu, jež je základem alergických fenotypů. Souhrn: V rozsáhlých GWAS byly objeveny nové genetické varianty související s alergickou rýmou a alergickými fenotypy. Charakteristika genetického základu nám poskytuje náhled na možné cíle budoucích studií a odpovídající léčebné postupy.
- MeSH
- alergická rýma * genetika MeSH
- celogenomová asociační studie MeSH
- DNA vazebné proteiny * genetika MeSH
- enzymy opravy DNA * genetika MeSH
- genetická predispozice k nemoci MeSH
- interleukin-1 * genetika MeSH
- interleukin-13 * genetika MeSH
- interleukiny * genetika MeSH
- lidé MeSH
- membránové proteiny * genetika MeSH
- receptory interleukinu-1 - typ I * genetika MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- přehledy MeSH
OBJECTIVES: Gastroesophageal reflux (GERD) is a one of the major public health problem that can lead to reflux esophagitis (RE), Barrett's esophagus (BE), and esophageal adenocarcinoma (EAC). The aim of our study was to determine the impact of IL-1 gene polymorphisms on the development of GERD, RE and BE. METHODS: Three hundred and thirty-three Czech patients with gastroesophageal reflux and 165 healthy controls were included in this case-control study. Four polymorphisms in the genes of the IL-1 cluster [IL-1A(-889C/T), IL-1B(-511C/T), IL-1B(+3953C/T), and IL-1RN(VNTR)] were analyzed. RESULTS: Significant differences were found in IL-1RN 1/2 genotype between patients with GERD/RE and controls and in IL-1B+3953 T allele between patients with BE and healthy subjects. In addition, complex analysis revealed differences in IL-1 haplotype frequencies between the groups. Specifically, the haplotype TCCL was significantly more frequent (p = 0.016) in GERD patients than in controls and the haplotype CCCL more frequent (p = 0.008) in RE patients than in controls. However, in patients with BE, frequency of haplotype TCTL was lower (p = 0.05) and haplotypes CTCL and TCCL were higher (p = 0.03 and p = 0.02) in comparison with the controls. CONCLUSIONS: Our results suggest that IL-1 haplotypes may be associated with susceptibility to GERD, RE and BE.
- MeSH
- Barrettův syndrom genetika imunologie MeSH
- dospělí MeSH
- frekvence genu MeSH
- gastroezofageální reflux genetika imunologie MeSH
- genetické asociační studie MeSH
- genotyp MeSH
- haplotypy MeSH
- interleukin-1 genetika MeSH
- lidé středního věku MeSH
- lidé MeSH
- multigenová rodina imunologie MeSH
- studie případů a kontrol MeSH
- zvířata MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Geografické názvy
- Česká republika MeSH
The research objective was to establish a role of polymorphism of interleukin-1β gene in the locus 3954 (rs 1143634) on the chromosome 2q13-21 as a risk factor of an adverse course of the inflammatory process at chronic adenoiditis. The research is a part of the complex scientific subject "Translational Otorhinolaryngology" which was carried out in 2010-2012. The results of genotyping of 944 people were received. High total frequency of inheritance of mutant polymorphic allelic variants of interleukin-1β gene, including homozygous (C/C) and heterozygous (С/Т) carriage is revealed at children with chronic adenoiditis. The frequency was 95,5% in sampling. At a homozygous carriage of oligonucleotide replacement of thymine for cytosine in the position 3954 of interleukin-1β gene functional activity of interleukin-1β changed- its pro-inflammatory effect increased by 100%. Children of this group had a heavy current chronic adenoiditis with the frequent aggravations, complications and the interfacing diseases at high concentration in blood serum interleukin-1β (298,4±8,2) pg/ml (control − 65,43 pg/ml) (p˂0,001).
