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Plasma Levels Of T Helper 17 Cell-related Cytokines And Polymorphisms Of IL-6, IL-23R Genes In Residents Living In The Vicinity Of An Waste Incinerator

Posted on:2015-09-07Degree:MasterType:Thesis
Country:ChinaCandidate:Q HuoFull Text:PDF
GTID:2191330464459760Subject:Public Health
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Toxics, such as PCDD/Fs and heavy metals, can be produced and partly released into the atmosphere by fly-ash and stack emissions when municipal solid waste (MSW) is burned. These environmental pollutants can migrate across environmental boundaries reaching different media:soil, water, biota and vegetation. As a result, human health can be directly or indirectly affected through different pathways such as drinking water and contaminated foodstuffs, as well as through skin absorption. Human long-term environmentally exposured waste incineration pollutants may lead to immunity imbalance, abnormal activation of T-lymphocyte subsets, and eventually may induce chronic inflammation or even the onset of autoimmune diseases. Th17 cells as the primary effector cell type play an important role in clearing pathogens during host defense reactions and in inducing tissue inflammation in autoimmune disease.However, few studies paid attention to the plasma levels of T helper 17-related cytokines and polymorphisms of IL-6, IL-23R genes in residents living in the vicinity of an waste incinerator, so by studying these it may provide references for health risk assessment.In this study, we used questionnaire and blood test to investigate a totle of 307 residents which have been lived in local area more than 6 years. According to the prevailing wind direction throughout the year, we recruited 100 residents from a zone within 10km downwind from the waste incinerator as high exposure group (near group) and 100 residents from a zone beyond 10km downwind from the waste incinerator without known industrial pollution sources as control group (far group). Between the above two zones, we also recruited 107 residents as the middle exposure group.CYP1A1 gene expressions in participants’ leukocytes were determined with semi-quantitative reverse transcriptase polymerase chain reaction, and plasma cytokine levels were measured by Bio-PlexTM Cytokine Panel. Pyrosequencing technique were used to detect polymorphism of 4 polymorphisms of 2 genes, including IL-6, IL-23R genes.The results showed that, relative CYP1A1 mRNA levels in the high exposure group were significantly higher than those in the control group(P<0.05).After adjusting for age, body mass index(BMI), smoking, and alcohol consumption, the relative CYP1A1 mRNA levels were associated with zone category(β=0.03, P=0.002) in the mutilinear regression analyses.Levels of Th17-related cytokines were measured by Bio-PlexTM Cytokine Panel. The results showed that, the median IL-6, IL-17A, IL-17F, IL-22, and IL-23 levels were 4.44pg/mL,3.43pg/mL,41.38pg/mL,19.34pg/mL,51.15 pg/mL respectively in the high exposure group, and 3.31pg/mL,2.33pg/mL,22.99 pg/mL,9.58pg/mL, 31.26pg/mL in the middle exposure group separately, and 3.14 pg/mL,2.17pg/mL, 25.52pg/mL,7.97pg/mL,21.60 pg/mL in the control group. Both of nonparametric test and multiple linear regression showed that the plasma levels of IL-6, IL-17A, IL-17F, IL-22, and IL-23 in the high exposure group were significantly higher than those in the control group(P<0.05). Smoke was also suggested to be an influential factor in the mutilinear regression analyses of In-transformed concentrations of IL-6, IL-17A, IL-17F, IL-22, and IL-23. And sex can be another related factor in the multiple linear regression analysis of In-transformed concentrations of IL-17A, IL-17F, and IL-23 with zone category and smoke.We analyzed the relationships of genotypes, haplotypes with plasma levels of Th17-related cytokines. No significant differences were observed in the IL-6 plasma levels between different genotypes of the rsl 800796 polymorphism in IL-6 gene. And, there were no significant differences in the IL-17A, IL-17F, IL-22 plasma levels between different genotypes of each polymorphisms of IL-23R gene, including rs7517847, rs1343151, rs11209032. Then, we used multiple linear regression analysis to analyze the relationship between polymorphism and susceptibilities to toxicities. After adjusting for other factors, we found that those who carry IL-23R gene GCA haplotype had higher IL-17A levels in plasma than those who carried wild-type TCG haplotype(β=0.63, P=0.036); plasma levels of IL-17A of participants carrying IL-23R gene GCG haplotype was higer than those with wild-type TCG haplotype (P=0.50, P=0.012).In conclusion, the plasma levels of IL-6, IL-17A, IL-17F, IL-22, and IL-23 in residents living in the vicinity of the waste incineration are remarkably higher than those of the residents lived further away from the waste incinerator. As one of the susceptible factors, IL-23R gene polymorphisms have a certain relationship with the changes of the IL-17A plasma levels. No significant differences were observed in the plasma levels of IL-6 between different genotypes of the rs1800796 polymorphism.
Keywords/Search Tags:waste incineration pollutallts, CYP1A1, genetic polymorphisms, cytokine, IL-6, IL-17A, IL-17F, IL-22, IL-23
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