Dataset Information

The Association of Serum TNF-? Levels and Blood Multi-Elements Modified by TNF-? Gene Polymorphisms in Metal Industrial Workers.

ABSTRACT: Health of the metal industrial workers should be a noteworthy issue due to the hazard ofchronic exposure to metals or toxic elements. The interactions among multiple elements aresophisticated and may differ from person to person. Tumor necrosis factor-? (TNF-?) genepolymorphisms were supposed to be involved with the interactions because TNF-? plays animportant role in inflammation, a mechanism by which toxic elements cause threats to humanhealth. This research aimed to analyze the influence of TNF-? gene polymorphisms and multielementson serum TNF-? level. Blood multi-elements concentrations (lead, cadmium, arsenic,selenium, cobalt, copper, and zinc), serum TNF-? level, and TNF-? single nucleotidepolymorphisms (SNPs), including -238G > A (rs361525), -308G > A (rs1800629), -857C > T(rs1799724), -863C > A (rs1800630), and -1031T > C (rs1799964), were measured in 462 metalindustrial workers. We applied mixed-effect models to analyze the interactions among multielementsand TNF-? SNPs. Blood concentration of all elements were positively associated withserum TNF-? level, and the effects may be modified by TNF-? gene polymorphisms. Our studyrevealed that TNF-? -308A/A and -1031C/C may be susceptible genotypes, and thus we suggestthat those workers should take preventive measures against metal toxicity.

SUBMITTER: Chen TH

PROVIDER: S-EPMC6862333 | biostudies-literature | 2019 Oct

REPOSITORIES: biostudies-literature

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The Association of Serum TNF-α Levels and Blood Multi-Elements Modified by TNF-α Gene Polymorphisms in Metal Industrial Workers.

Chen Tzu-Hua TH Huang Joh-Jong JJ Kung Wei-Shyang WS Lee Su-Shin SS Sun Hung-Yu HY Chuang Hung-Yi HY

International journal of environmental research and public health 20191023 21

Health of the metal industrial workers should be a noteworthy issue due to the hazard ofchronic exposure to metals or toxic elements. The interactions among multiple elements aresophisticated and may differ from person to person. Tumor necrosis factor-α (<i>TNF-α</i>) <i>gene</i>polymorphisms were supposed to be involved with the interactions because TNF-α plays animportant role in inflammation, a mechanism by which toxic elements cause threats to humanhealth. This research aimed to analyze the ...[more]

PMID: 31652851

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Project description:Background and aimsAlcoholic liver disease (ALD) is the leading cause of the liver cirrhosis related death worldwide. Excessive alcohol consumption resulting enhanced gut permeability which trigger sensitization of inflammatory cells to bacterial endotoxins and induces secretion of cytokines, chemokines leading to activation of stellate cells, neutrophil infiltration and hepatocyte injury followed by steatohepatitis, fibrosis and cirrhosis. But all chronic alcoholics are not susceptible to ALD. This study investigated the causes of differential immune responses among ALD patients and alcoholic controls (ALC) to identify genetic risk factors and assessed the therapeutic potential of a microRNA, miR-124-3p.Materials and methodsBio-Plex Pro™ Human Chemokine analysis/qRT-PCR array was used for identification of deregulated immune genes. Sequencing/luciferase assay/ELISA detected and confirmed the polymorphisms. THP1 co-cultured with HepG2/LX2/HUVEC and apoptosis assay/qRT-PCR/neutrophil migration assay were employed as required.ResultsThe combined data analysis of the GSE143318/Bio-Plex Pro™ Human Chemokine array and qRT-PCR array revealed that six genes (TNFα/IL1β/IL8/MCP1/IL6/TGFβ) were commonly overexpressed in both serum/liver tissue of ALD-patients compared to ALC. The promoter sequence analysis of these 6 genes among ALD (n=322)/ALC (n=168) samples revealed that only two SNPs, rs361525(G/A) at -238 in TNF-α/rs1143627(C/T) at -31 in IL1β were independently associated with ALD respectively. To evaluate the functional implication of these SNPs on ALD development, the serum level of TNF-α/IL1β was verified and observed significantly higher in ALD patients with risk genotypes TNF-α-238GA/IL1β-31CT+TT than TNF-α-238GG/IL1β-31CC. The TNF-α/IL1β promoter Luciferase-reporter assays showed significantly elevated level of luciferase activities with risk genotypes -238AA/-31TT than -238GG/-31CC respectively. Furthermore, treatment of conditioned medium of TNF-α/IL1β over-expressed THP1 cells to HepG2/LX2/HUVEC cells independently showed enhanced level of ER stress and apoptosis in HepG2/increased TGFβ and collagen-I production by LX2/huge neutrophil infiltration through endothelial layer. However, restoration of miR-124-3p in THP1 attenuated such inter-cellular communications and hepatocyte damage/collagen production/neutrophil infiltration were prohibited. Target analysis/luciferase-reporter assays revealed that both TNF-α/IL1β were inhibited by miR-124-3p along with multiple genes from TLR4 signaling/apoptosis/fibrogenesis pathways including MYD88, TRAF3/TRADD, Caspase8/PDGFRA, TGFβR2/MCP1, and ICAM1 respectively.ConclusionThus, rs361525(G/A) in TNF-α and rs1143627(C/T) in IL1β gene may be used as early predictors of ALD susceptibility among East Indian population. Impeding overexpressed TNF-α/IL1β and various genes from associated immune response pathways, miR-124-3p exhibits robust therapeutic potential for ALD patients.

Dataset Information

The Association of Serum TNF-? Levels and Blood Multi-Elements Modified by TNF-? Gene Polymorphisms in Metal Industrial Workers.

Publications

The Association of Serum TNF-α Levels and Blood Multi-Elements Modified by TNF-α Gene Polymorphisms in Metal Industrial Workers.

Similar Datasets

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