scholarly journals Toll-Like Receptor 4 Wild Type Homozygozity of Polymorphisms +896 and +1196 Is Associated with High Gastrin Serum Levels and Peptic Ulcer Risk

PLoS ONE ◽  
2015 ◽  
Vol 10 (7) ◽  
pp. e0131553 ◽  
Author(s):  
Vesa-Matti Pohjanen ◽  
Olli-Pekka Koivurova ◽  
Heikki Huhta ◽  
Olli Helminen ◽  
Johanna M. Mäkinen ◽  
...  
Keyword(s):  
Peptic Ulcer ◽  
Serum Levels ◽  
Toll Like Receptor ◽  
Wild Type ◽  
Toll Like Receptor 4

scholarly journals Toll-like Receptor 4 Signaling in Ventilator-induced Diaphragm Atrophy

2012 ◽  
Vol 117 (2) ◽  
pp. 329-338 ◽  
Author(s):  
Willem-Jan M. Schellekens ◽  
Hieronymus W. H. van Hees ◽  
Michiel Vaneker ◽  
Marianne Linkels ◽  
P. N. Richard Dekhuijzen ◽  
...  
Keyword(s):  
Mechanical Ventilation ◽  
Caspase 3 ◽  
Toll Like Receptor ◽  
Wild Type ◽  
Toll Like Receptor 4 ◽  
Ubiquitin Proteasome Pathway ◽  
Ubiquitin Proteasome ◽  
Proteasome Pathway ◽  
Diaphragm Atrophy ◽  
Deficient Mice

Background Mechanical ventilation induces diaphragm muscle atrophy, which plays a key role in difficult weaning from mechanical ventilation. The signaling pathways involved in ventilator-induced diaphragm atrophy are poorly understood. The current study investigated the role of Toll-like receptor 4 signaling in the development of ventilator-induced diaphragm atrophy. Methods Unventilated animals were selected for control: wild-type (n = 6) and Toll-like receptor 4 deficient mice (n = 6). Mechanical ventilation (8 h): wild-type (n = 8) and Toll-like receptor 4 deficient (n = 7) mice.Myosin heavy chain content, proinflammatory cytokines, proteolytic activity of the ubiquitin-proteasome pathway, caspase-3 activity, and autophagy were measured in the diaphragm. Results Mechanical ventilation reduced myosin content by approximately 50% in diaphragms of wild-type mice (P less than 0.05). In contrast, ventilation of Toll-like receptor 4 deficient mice did not significantly affect diaphragm myosin content. Likewise, mechanical ventilation significantly increased interleukin-6 and keratinocyte-derived chemokine in the diaphragm of wild-type mice, but not in ventilated Toll-like receptor 4 deficient mice. Mechanical ventilation increased diaphragmatic muscle atrophy factor box transcription in both wild-type and Toll-like receptor 4 deficient mice. Other components of the ubiquitin-proteasome pathway and caspase-3 activity were not affected by ventilation of either wild-type mice or Toll-like receptor 4 deficient mice. Mechanical ventilation induced autophagy in diaphragms of ventilated wild-type mice, but not Toll-like receptor 4 deficient mice. Conclusion Toll-like receptor 4 signaling plays an important role in the development of ventilator-induced diaphragm atrophy, most likely through increased expression of cytokines and activation of lysosomal autophagy.

Association ofHelicobacter pyloriinfection with Toll-like receptor-4 Thr399Ile polymorphism increased the risk of peptic ulcer development in North of Iran

Apmis ◽  
2017 ◽  
Vol 126 (1) ◽  
pp. 76-84 ◽  
Author(s):  
Mehdi Tourani ◽  
Maryam Habibzadeh ◽  
Javad Shokri-Shirvani ◽  
Omid Teymournejad ◽  
Amrollah Mostafazadeh ◽  
...  
Keyword(s):  
Peptic Ulcer ◽  
Toll Like Receptor ◽  
Toll Like Receptor 4 ◽  
North Of Iran

scholarly journals Association of toll-like receptor 4, 5 and 10 polymorphisms with Helicobacter pylori -positive peptic ulcer disease in a center in Jordan

2021 ◽  
Vol 41 (4) ◽  
pp. 206-215
Author(s):  
Laith AL-Eitan ◽  
Fouad Abdelaziz Almomani ◽  
Sohaib Mahmoud Al-Khatib ◽  
Hanan Abdulraheem Aljamal ◽  
Mohammed Nayef Al-Qusami ◽  
...  
Keyword(s):  
Helicobacter Pylori ◽  
Peptic Ulcer ◽  
Conflicts Of Interest ◽  
Care Center ◽  
Treatment Success ◽  
Tertiary Care ◽  
Genotype Distribution ◽  
Toll Like Receptor ◽  
Toll Like Receptor 4 ◽  
H Pylori

BACKGROUND: Helicobacter pylori infection is widespread, affecting about 50% of the global population. Polymorphisms in host genes such as the toll-like receptor 4 ( TLR4 ) might affect the susceptibility and severity of infection and treatment success. OBJECTIVE: Investigate the susceptibility and severity of H pylori infection with host TLR4 (rs11536889, rs4986790, rs200109652, rs10759932), TLR5 (rs5744174, rs2072493, rs746250566), TLR10 (rs559182335, rs10004195) polymorphisms. DESIGN: Analytical, cross-sectional. SETTING: Endoscopy clinic at tertiary care center. PATIENTS AND METHODS: Genomic DNA was extracted from formalin-fixed paraffin-embedded tissues collected from H pylori -infected patients and healthy individuals. The single nucleotide polymorphisms (SNPs) within the targeted TLR genes were genotyped to assess the genetic association of various SNPs with disease severity. MAIN OUTCOME MEASURES: Effect of genotype distribution on H pylori infection. SAMPLE SIZE: 250 peptic ulcer patients and 217 controls. RESULTS: The TLR10 genotype showed no significant association with H pylori infection except for rs10004195 (T>A) ( P =.002). The genotype frequency of Rs5744174 in TLR5 had a significant association with the presence of H pylori infection ( P =.046, OR=0.52). Except for gender (P=.022), there were no significant associations between clinical and demographic variables and SNPs relating to the severity of the H pylori infections. CONCLUSIONS: Our findings are consistent with differences in severity of H pylori infection due to TLR SNPs in different ethnic groups. Understanding differences in genetic susceptibility could help in classifying patients and matching patients with various treatment options on a genetic basis. LIMITATIONS: Lack of H pylori pathogenicity features assessment. CONFLICTS OF INTEREST: None.

scholarly journals EVALUATION OF SERUM TOLL-LIKE RECEPTOR 4 AND NUCLEAR FACTOR-ΚBP65 PROTEINS IN ORAL SQUAMOUS CELL CARCINOMA

2018 ◽  
Vol 11 (12) ◽  
pp. 179
Author(s):  
Jayalalitha Sathiyamoorthy ◽  
Vidyarani Shyamsundar ◽  
N. Aravindha Babu ◽  
Subbaih Shanmugam ◽  
Jagadeesan. G. Mani ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Oral Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Pearson Correlation ◽  
Serum Levels ◽  
Study Groups ◽  
Nuclear Factor ◽  
Toll Like Receptor ◽  
Toll Like Receptor 4 ◽  
Pearson Correlation Test

Objective: The present study is aimed to estimate the serum toll-like receptor 4 (sTLR 4) and nuclear factor-κB (NF-κB) p65 proteins in patients of oral squamous cell carcinoma (OSCC). Methods: The study was performed in prospective cases of 22 OSCC patients, 10 oral epithelial dysplasia patients, 8 control with chewing habits, and 4 control patients. The estimation of sTLR 4 and NF-κBp65 proteins was done by enzyme-linked immunosorbent assay method. The Pearson correlation test was performed to find out the relationship between these two proteins. Results: There was an increase in the sTLR 4 protein level in study groups OSCC, oral premalignant disorders, control with chewing habits, and control habits such as 1.31 ng/ml±1.06 ng/ml, 1.99 ng/ml±0.98 ng/ml, and 2.11 ng/ml±0.61 ng/ml, respectively, when comparable (p=0.008) to control patients with 0.60 ng/ml±0.24 ng/ml. However, in the case of serum level NF-κBp65 protein all the study groups including the control showed same values. The Pearson correlation test showed significant relationship (rpearson=0.91, [p<0.0005]) of these two proteins only in the OSCC patients. Conclusion: It can be concluded that serum levels of TLR 4 are increased in OSCC patients, but there was no variation seen for the NF-κBp65 protein. There is a strong interrelationship exist between the serum levels of TLR 4 and NF-κBp65 proteins in the OSCC patients only.

Monosodium urate crystal interleukin-1β release is dependent on Toll-like receptor 4 and transient receptor potential V1 activation

Rheumatology ◽  
2019 ◽  
Author(s):  
Mateus F. Rossato ◽  
Carin Hoffmeister ◽  
Gabriela Trevisan ◽  
Fabio Bezerra ◽  
Thiago M. Cunha ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Synovial Fluid ◽  
Transient Receptor Potential ◽  
Receptor Potential ◽  
Acute Gout ◽  
Toll Like Receptor ◽  
Wild Type ◽  
Toll Like Receptor 4 ◽  
Transient Receptor ◽  
Nitrite Nitrate

AbstractObjectiveThe present study aimed to elucidate the mechanisms involved in MSU-induced IL-1β release in a rodent animal model of acute gout arthritis.MethodsPainful (mechanical and thermal hypersensitivity, ongoing pain and arthritis score) and inflammatory (oedema, plasma extravasation, cell infiltration and IL-1β release) parameters were assessed several hours after intra-articular injection of MSU (100 µg/articulation) in wild-type or knockout mice for Toll-like receptor 4 (TLR4), inducible nitric oxide synthase (iNOS), transient receptor potential (TRP) V1 and the IL-1 receptor (IL-1R). Also, wild-type animals were treated with clodronate, lipopolysaccharide from Rhodobacter sphaeroides (LPS-RS) (TLR4 antagonist), spleen tyrosine kinase (SYK) inhibitor (iSYK), aminoguanidine (AMG, an iNOS inhibitor) or SB366791 (TRPV1 antagonist). Nitrite/nitrate and IL-1β levels were measured on the synovial fluid of wild-type mice, 2 h after intra-articular MSU injections, or medium from macrophages stimulated for MSU (1000 μg) for 2 h.ResultsIntra-articular MSU injection caused robust nociception and severe inflammation from 2 up to 6 h after injection, which were prevented by the pre-treatment with clodronate, LPS-RS, iSYK, AMG and SB366791, or the genetic ablation of TLR4, iNOS, TRPV1 or IL-1R. MSU also increased nitrite/nitrate and IL-1β levels in the synovial fluid, which was prevented by clodronate, LPS-RS, iSYK and AMG, but not by SB366791. Similarly, MSU-stimulated peritoneal macrophages released nitric oxide, which was prevented by LPS-RS, iSYK and AMG, but not by SB366791, and released IL-1β, which was prevented by LPS-RS, iSYK, AMG and SB366791.ConclusionOur data indicate that MSU may activate TLR4, SYK, iNOS and TRPV1 to induce the release of IL-1β by macrophages, triggering nociception and inflammation during acute gout attack.

The phytosphingosine-CD300b interaction promotes zymosan-induced, nitric oxide–dependent neutrophil recruitment

2019 ◽  
Vol 12 (564) ◽  
pp. eaar5514 ◽  
Author(s):  
Mariko Takahashi ◽  
Kumi Izawa ◽  
Makoto Urai ◽  
Yoshinori Yamanishi ◽  
Akie Maehara ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Neutrophil Recruitment ◽  
No Production ◽  
Dependent Manner ◽  
Toll Like Receptor ◽  
Wild Type ◽  
Neutrophil Accumulation ◽  
Toll Like Receptor 4 ◽  
Potential Ligand ◽  
Inflammatory Dendritic Cells

Zymosan is a glucan that is a component of the yeast cell wall. Here, we determined the mechanisms underlying the zymosan-induced accumulation of neutrophils in mice. Loss of the receptor CD300b reduced the number of neutrophils recruited to dorsal air pouches in response to zymosan, but not in response to lipopolysaccharide (LPS), a bacterial membrane component recognized by Toll-like receptor 4 (TLR4). An inhibitor of nitric oxide (NO) synthesis reduced the number of neutrophils in the zymosan-treated air pouches of wild-type mice to an amount comparable to that inCD300b−/−mice. Treatment with clodronate liposomes decreased the number of NO-producing, CD300b+inflammatory dendritic cells (DCs) in wild-type mice, thus decreasing NO production and neutrophil recruitment. Similarly, CD300b deficiency decreased the NO-dependent recruitment of neutrophils to zymosan-treated joint cavities, thus ameliorating subsequent arthritis. We identified phytosphingosine, a lipid component of zymosan, as a potential ligand of CD300b. Phytosphingosine stimulated NO production in inflammatory DCs and promoted neutrophil recruitment in a CD300b-dependent manner. Together, these results suggest that the phytosphingosine-CD300b interaction promotes zymosan-dependent neutrophil accumulation by inducing NO production by inflammatory DCs and that CD300b may contribute to antifungal immunity.

scholarly journals Differential Activation of Human and Mouse Toll-Like Receptor 4 by the Adjuvant Candidate LpxL1 of Neisseria meningitidis

2008 ◽  
Vol 76 (8) ◽  
pp. 3801-3807 ◽  
Author(s):  
Liana Steeghs ◽  
A. Marijke Keestra ◽  
Andries van Mourik ◽  
Heli Uronen-Hansson ◽  
Peter van der Ley ◽  
...  
Keyword(s):  
Neisseria Meningitidis ◽  
Lipid A ◽  
Vaccine Development ◽  
Meningococcal Vaccine ◽  
Toll Like Receptor ◽  
Wild Type ◽  
Toll Like Receptor 4 ◽  
Species Specific ◽  
Human And Mouse ◽  
Dc Maturation

ABSTRACT Neisseria meningitidis LpxL1 lipopolysaccharide (LPS) bearing penta-acylated lipid A is considered a promising adjuvant candidate for inclusion in future N. meningitidis vaccines, as it elicits a markedly reduced endotoxic response in human macrophages relative to that in wild-type (hexa-acylated) LPS, while it is an equally effective adjuvant in mice. As dendritic cells (DC) and Toll-like receptors (TLR) are regarded as central mediators in the initiation of an immune response, here we evaluated the ability of LpxL1 LPS to mature and to activate human DC and examined its TLR4-/MD-2-activating properties. Unexpectedly, purified LpxL1 LPS displayed minimal human DC-stimulating properties compared to wild-type LPS. Although whole bacteria induced DC maturation and activation irrespective of their type of LPS, the LpxL1 mutant failed to activate the human recombinant TLR4/MD-2 complex expressed in HeLa cells. Similarly, purified LpxL1 LPS was unable to activate human TLR4/MD-2 and it even acted as an antagonist of wild-type LPS. Both wild-type and LpxL1 LPSs activated the murine TLR4/MD-2 complex, consistent with their abilities to induce maturation and activation of murine DC. Assays with cells transfected with different combinations of human and murine TLR4 and MD-2 indicated that TLR4 was a more-major determinant of the LPS response than MD-2. The species-specific activation of the TLR4/MD-2 complex by LpxL1 LPS may have an impact on the use of LpxL1 LPS as an adjuvant and the use of murine immunization models in human meningococcal vaccine development.

Toll-Like Receptor 4 Mediates Heme Induced Acute Lung Injury: Preclinical Study of Resatorvid in Sickle Cell Disease

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 2113-2113 ◽  
Author(s):  
Samit Ghosh ◽  
Olufolake Adisa ◽  
Yu Yang ◽  
Fang Tan ◽  
Solomon F Ofori-Acquah
Keyword(s):  
Acute Lung Injury ◽  
Sickle Cell Disease ◽  
Lung Injury ◽  
Sickle Cell ◽  
Acute Chest Syndrome ◽  
Toll Like Receptor ◽  
Wild Type ◽  
Cell Disease ◽  
Toll Like Receptor 4 ◽  
Breath Rate

Abstract Abstract 2113 Sickle cell disease (SCD) is characterized by multiple exacerbating events that cause intravascular hemolysis. Heme released into the circulation is scavenged by multiple plasma proteins and delivered to the liver for degradation. Our recent data indicate that this process is impaired in SCD resulting in excess protein-free plasma heme (PFPH) that triggers a lethal form of acute lung injury (ALI) in mice. In this study, we tested the hypothesis that toll-like receptor 4 (TLR4) mediates heme-induced ALI. Wild-type and two TLR4 mutant strains (B6.B10ScN-Tlr4lps-del/JthJ and C3H/HeJ) were intravenously injected with a dose range of ferric heme (0–210 micromoles/kg) and respiratory function monitored using a pulse oximeter. Excess PFPH was associated with reductions in oxygen saturation (SpO2) and breath rate in the wild-type mice but not in the TLR4 variants. Lungs of heme-treated wild-type mice were congested, edematous, hemorrhagic, and had thickened alveolar walls, while no histological abnormalities were found in the TLR4 variants. All heme-treated wild-type mice succumbed within 2 hours, while all TLR4 variants survived. Transgenic mice expressing exclusively human sickle hemoglobin (SS) were intravenously injected with a small molecule TLR4 inhibitor (resatorvid/TAK-242), or a lipid vehicle prior to induction of lung injury with heme (35 micromoles/kg). TAK-242 preserved lung function in the majority of SS mice that failed to scavenge excess PFPH, while both SpO2 and breath rate deteriorated in vehicle treated mice. The unique response to heme by TAK-242 and vehicle-treated SS mice was supported by histological analysis and survival (TAK-242; 76.9% vehicle; 23.5%, n=13–17; log-rank survival test, p<0.01). We provide the first evidence that the interaction between heme and TLR4 can be pathological, specifically causing a lethal form of ALI. Our data on TAK-242, a phase II drug, offers an attractive option to explore TLR4 inhibition as a novel therapeutic strategy to limit progression of acute chest syndrome. Disclosures: Ofori-Acquah: Emory University: Patents & Royalties.

scholarly journals TACI και σήψη σε βαρέως πάσχοντες ασθενείς στη ΜΕΘ

2014 ◽  
Author(s):  
Μαρία Κομπότη
Keyword(s):  
Sofa Score ◽  
Hazard Ratio ◽  
Apache Ii ◽  
Apache Ii Score ◽  
Toll Like Receptor ◽  
Wild Type ◽  
Odds Ratios ◽  
Toll Like Receptor 4 ◽  
Pcr Rflp

Σκοπός: ο προσδιορισμός των γενετικών πολυμορφισμών των μορίων TACI, BAFF και TLR4 και η διερεύνηση πιθανής συσχέτισής τους με την εμφάνιση σήψης και τη θνητότητα σε ασθενείς που εισάγονται στη ΜΕΘ. Ασθενείς-Μέθοδος: Προοπτική μελέτη παρακολούθησης όλων των ασθενών που εισήχθησαν στη Μονάδα Εντατικής Θεραπείας μέχρι την έκβαση (έξοδος, θάνατος). Για τη φυσική ανοσία μελετήθηκαν δύο πολυμορφισμοί του toll-like receptor 4 (ΤLR4-D299G και TLR4-T399I) και ένας πολυμορφισμός του C2 που προκαλεί ανεπάρκεια συμπληρώματος (C2del28bp). Για την επίκτητη ανοσία μελετήθηκαν δύο πολυμορφισμοί του BAFF-R (BAFF-R-H159Y και BAFF-R-P21R) και ένας του TACI (TACI-C104R). Η ανίχνευση των πολυμορφισμών έγινε με αλυσιδωτή αντίδραση πολυμεράσης και ανάλυση με ενδονουκλεάσες περιορισμού (PCR-RFLP). Αποτελέσματα: Στη μελέτη συμπεριελήφθησαν 215 ασθενείς (148 άνδρες και 67 γυναίκες). Η ηλικία (μέσος ± SD) ήταν 54,1±19,7 έτη, APACHE II score εισαγωγής στη ΜΕΘ 22,0±6,0 και SOFA score εισαγωγής στη ΜΕΘ 9,7±3,5. Σήψη στη ΜΕΘ βρέθηκε σε 108 ασθενείς (50,2%) και η θνητότητα στη ΜΕΘ ήταν 20,5% [95% διάστημα αξιοπιστίας 15,0–25,9]. Οι SNPs του TLR4 βρέθηκαν σε συζευγμένη κατάσταση. Οι φορείς κάποιου TLR4 SNP και οι φορείς του BAFFR-P21R συσχετίστηκαν ανεξάρτητα με χαμηλότερη πιθανότητα σήψης στη ΜΕΘ συγκριτικά με τους wild-type ομοζυγώτες [διορθωμένα odds ratios 0,32, 95%CI 0,12–0,86, p=0,024 για τον TLR4-T399I, 0,34, 95%CI 0,13–0,94, p=0,037 για τον TLR4-T399I and 0,44, 95%CI 0,20–0,97, p=0,044 για τον BAFFR-P21R]. Από την ανάλυση υποομάδων, φάνηκε ότι η συσχέτιση αυτή αφορούσε στους παθολογικούς ασθενείς και οριακά στους τραυματίες, ενώ στους χειρουργικούς ασθενείς δεν παρατηρήθηκε συσχέτιση. Η φορεία του TACI-C104R SNP είχε καλή προβλεπτική αξία μετά από διόρθωση ως προς συγχυτικούς παράγοντες [hazard ratio 5,01 (1,14–22,03, p=0,033). Ο BAFFR-H159Y SNP δεν συσχετίστηκε με την εμφάνιση σήψης και τη θνητότητα, ενώ ο πολυμορφισμός C2del28bp δεν ανευρέθηκε στο δείγμα της μελέτης.Συμπεράσματα: Η μελέτη μας έδειξε ότι σε βαρέως πάσχοντες ασθενείς ΜΕΘ, οι πολυμορφισμοί TLR4-D299G (rs4986790), TLR4-T399I (rs4986791) και TNFRSF13C/BAFFR-P21R (rs77874543) ασκούν προστατευτική επίδραση αναφορικά με την εμφάνιση σήψης, ενώ ο πολυμορφισμός TNFRSF13B/TACI-C104R (rs34557412) συσχετίζεται σημαντικά με αύξηση της θνητότητας στη ΜΕΘ. Ο πολυμορφισμός TNFRSF13C/BAFFR-H159Y (rs61756766) δεν συσχετίστηκε με την εμφάνιση σήψης ή τη θνητότητα στη ΜΕΘ. Διαπιστώθηκε ανισορροπία σύνδεσης για τους πολυμορφισμούς TLR4-D299G (rs4986790) και TLR4-T399I (rs4986791) και για τους πολυμορφισμούς TNFRSF13C/BAFFR-P21R (rs77874543) και TNFRSF13C/BAFFR-H159Y (rs61756766). Ο πολυμορφισμός C2-c.841_849+19del28 (rs9332736) δεν ανιχνεύτηκε στο δείγμα των ασθενών της μελέτης.

Sign in / Sign up

Export Citation Format

Share Document