Epistatic effect of TLR-1, -6 and -10 polymorphisms on organic dust-mediated cytokine response

Smith, Lynette M.; Weissenburger-Moser, Lisa; Heires, Art J.; Bailey, Kristina L.; Romberger, Debra J.; LeVan, Tricia D.

doi:10.1038/gene.2016.51

Cited by 11 publications

(8 citation statements)

References 42 publications

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“…Childhood IgAN and PIU had the same susceptible genotype (AA genotype), while the TA genotype and a dominant model (AA/TA vs TT) were associated with childhood IgAN. TLR10 rs11725309 (dominant model,CC/TC vs TT) was found to be associated with organic dust-mediated cytokine response, 40 , while the CC genotype was related to PIU in our study. Other studies showed that rs6841698 (G allele) contributed to susceptibility to CD.…”

Section: Discussionsupporting

confidence: 47%

Association of toll-like receptor 10 polymorphisms with paediatric idiopathic uveitis in Han Chinese

Tan

Deng

et al. 2019

Br J Ophthalmol

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AimsWe aimed to determine whether paediatric idiopathic uveitis (PIU) and juvenile idiopathic arthritis associated paediatric uveitis (JIA-PU) have an association with Toll-like receptor 10 (TLR10) gene polymorphisms in Han Chinese.MethodsTen tag single nucleotide polymorphisms (SNPs) of TLR10 were analysed in 992 PIU patients, 127 JIA-PU patients and 1600 controls using the Sequenom MassARRAY system and iPLEX Gold assay. Genotype and allele frequencies were analysed using the χ2 test. A stratified analysis was performed according to the clinical features of PIU.ResultsIncreased frequencies of the rs2101521 A allele, rs10004195 A allele, rs11725309 CC genotype and rs6841698 AA genotype were found in PIU patients compared with controls (corrected p values (Pc)=1.81×10-4, Pc= 1.12×10-2, Pc=2.41×10-2 and Pc=3.29×10-3, respectively). There was no association between these 10 tag SNPs and JIA-PU. In the stratified analysis, the frequency of the rs6841698 A allele was higher in PIU patients with cataract (Pc=1.45×10-6). The frequencies of the rs2101521 A allele and rs6841698 AA genotype were increased in PIU patients with band keratopathy (BK) (Pc=2.32×10-2, Pc=3.30×10-3, respectively).ConclusionTLR10 gene polymorphisms (rs2101521, rs10004195, rs11725309 and rs6841698) confer susceptibility to PIU in Han Chinese. In a stratified analysis, rs2101521 and rs6841698 are associated with PIU with BK, and rs6841698 correlates with PIU with cataract.

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Section: Discussionsupporting

confidence: 47%

Association of toll-like receptor 10 polymorphisms with paediatric idiopathic uveitis in Han Chinese

Tan

Deng

et al. 2019

Br J Ophthalmol

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“…Blood was obtained by venipuncture and used for a cell differential and the whole blood assay [ 26 ]. Heparinized blood samples were processed within 2 h of collection.…”

Section: Methodsmentioning

confidence: 99%

“…For IL-6 and TNF-α measurement, a sandwich ELISA was employed [ 26 ]. In brief, purified (goat) anti-human IL-6 or (mouse) anti-human TNF-α antibody (both from R&D Systems, Minneapolis, MN) were used to coat a microtiter plate overnight.…”

Section: Methodsmentioning

confidence: 99%

Relationship of systemic IL-10 levels with proinflammatory cytokine responsiveness and lung function in agriculture workers

et al. 2018

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BackgroundAgriculture workers are exposed to microbial component- and particulate matter-enriched organic dust aerosols. Whereas it is clear that exposure to these aerosols can lead to lung inflammation, it is not known how inflammatory responses are resolved in some individuals while others develop chronic lung disease. Interleukin (IL)-10 is an immunomodulatory cytokine that is recognized as a potent anti-inflammatory and pro-resolving factor. The objective of this study was to determine whether there is a relationship of systemic IL-10 and proinflammatory responses and/or respiratory health effects in humans with prior agriculture exposure.MethodsThis is a cross sectional study of 625 veterans with > 2 years of farming experience. Whole blood was stimulated with or without organic dust and measured for IL-6, TNFα and IL-10. Participants underwent spirometry and respiratory symptoms were assessed by questionnaire.ResultsWe found that baseline IL-10 concentration from the whole blood assay was inversely associated with ΔTNF-α (r = − 0.63) and ΔIL-6 (r = − 0.37) levels. Results remained highly significant in the linear regression model after adjusting for age, sex, BMI, race, education, smoking status, and white blood cell count (ΔTNF-α, p < 0.0001; ΔIL-6, p < 0.0001). We found no association between chronic cough (p = 0.18), chronic phlegm (p = 0.31) and chronic bronchitis (p = 0.06) and baseline IL-10 levels using univariate logistic regression models. However, we did find that higher FEV1/FVC was significantly associated with increased baseline IL-10 concentration.ConclusionsCollectively, these studies support a potential role for IL-10 in modulating an inflammatory response and lung function in agriculture-exposed persons.

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“…Necroptosis is a form of regulated cell death generally manifested with a necrotic morphology, which is initiated by signals from the microenvironment that can be detected by specific death receptors, such as TNFR1 and FAS 28–33, or receptors for pathogen recognition, such as DAI, TLR3 and TLR4 34 35 36, 37. Engagement of death receptors triggers the activation of the receptor-interacting protein kinase 1 (RIPK1), which autophosphorylates and recruits RIPK3 through RIP homotypic interaction motif (RHIM) domains present on both kinases 38.…”

Section: Cell Death Modalitiesmentioning

confidence: 99%

Cell death pathologies: targeting death pathways and the immune system for cancer therapy

et al. 2018

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Alterations in the molecular mechanisms of cell death are a common feature of cancer. These alterations enable malignant cells to survive intrinsic death signalling leading to accumulation of genetic aberrations and helping them to cope with adverse conditions. Regulated cell death has historically been exclusively associated with classical apoptosis; however, increasing evidence indicates that several alternative mechanisms orchestrate multiple death pathways, such as ferroptosis, entosis, necroptosis and immunogenic cell death, each with distinct underlying molecular mechanisms. Although pharmacological targeting of cell death pathways has been the subject of intensive efforts in recent decades with a dominant focus on targeting apoptosis, the identification of these novel death pathways has opened additional venues for intervention in cancer cells and the immune system. In this mini-review, we cover some recent progress on major recently emerged cell death modalities, emphasizing their potential clinical and therapeutic implications. We also discuss the interplay between cell death and immune response, highlighting the potential of the combination of traditional anticancer therapy and immunocheckpoint blockade. While attempting to stimulate discussion and draw attention to the possible clinical impact of these more recently emerged cell death modalities, we also cover the major progress achieved in translating strategies for manipulation of apoptotic pathways into the clinic, focusing on the attempts to target the anti-apoptotic protein BCL-2 and the tumour suppressor p53.

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Epistatic effect of TLR-1, -6 and -10 polymorphisms on organic dust-mediated cytokine response

Cited by 11 publications

References 42 publications

Association of toll-like receptor 10 polymorphisms with paediatric idiopathic uveitis in Han Chinese

Association of toll-like receptor 10 polymorphisms with paediatric idiopathic uveitis in Han Chinese

Relationship of systemic IL-10 levels with proinflammatory cytokine responsiveness and lung function in agriculture workers

Cell death pathologies: targeting death pathways and the immune system for cancer therapy

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