The role of interleukin family in perfluorooctanoic acid (PFOA)-induced immunotoxicity

Zhang, Hangjun; Fang, Wendi; Wang, Dandan; Gao, Nana; Ding, Ying; Chen, Chao

doi:10.1016/j.jhazmat.2014.08.043

Cited by 39 publications

(16 citation statements)

References 73 publications

(67 reference statements)

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“…To name a few, perfluorooctane sulfonate (PFOS) and 8:2 FTOH treatment reduced the content of IL‐6 and IL‐10 in the culture medium of human peripheral blood leukocytes . In zebrafish, PFOA can stimulate pro‐inflammatory cytokines at a low concentration of exposure (0.05 mg/L) and inhibit pro‐inflammatory cytokines at higher exposure concentrations (≥0.1 mg/L), with the trends being that PFOA‐induced IL secretion has a relationship with an antibody‐secreting trend . Our results indicated that 8:2 FTOH may lead to immune disturbances through the downregulation of cytokines.…”

Section: Discussionmentioning

confidence: 82%

8:2 Fluorotelomer alcohol causes immunotoxicity and liver injury in adult male C57BL/6 mice

Wang

Kong

et al. 2018

Environmental Toxicology

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8:2 Fluorotelomer alcohol (8:2 FTOH) is widely used in houseware and industrial goods and is ubiquitous in the surrounding environment. 8:2 FTOH has been linked to hepatoxicity, nephrotoxicity, and reproductive toxicity, as well as endocrine-disrupting effects. However, as of yet, the research regarding immunotoxicity of 8:2 FTOH remains largely limited. In the present study, adult male C57BL/6 mice were administered with 10, 30, and 100 mg/kg/d 8:2 FTOH by gavage for 28 days to investigate its immunotoxicity in vivo. The results showed that exposure to 8:2 FTOH caused increases in liver weight and histological changes in the liver, including vacuolation, cell swelling, immune cell infiltration, karyopyknosis and nuclear swelling. No histological change in either the spleen or the thymus was observed after administration of 8:2 FTOH. In addition, exposure to 8:2 FTOH reduced the concentration of IL-1β in serum, and mRNA levels of IL-1β, IL-6, and TNF-α in both the thymus and spleen. CXCL-1 mRNA expression was downregulated in both the liver and thymus after 8:2 FTOH administration, while only IL-1β mRNA expression was upregulated in the liver. Moreover, the exposure of primary cultured splenocytes to 8:2 FTOH inhibited the ConA-stimulated proliferation of splenocytes at concentrations of 30 and 100 μM, and the LPS-stimulated proliferation of splenocytes at 100 μM. Furthermore, 8:2 FTOH inhibited the level of secreted IFN-γ in ConA-stimulated splenocytes. The results obtained in the study demonstrated that 8:2 FTOH posed potential immunotoxicity and liver injury in mice. Our findings will provide novel data for the health risk assessment of 8:2 FTOH. K E Y W O R D S 8:2 FTOH, immunotoxicity, liver injury, mice, oxidative stress 1 | INTRODUCTION Fluorotelomers, as fluorocarbon-based oligomers or telomers, have various applications in food packaging, home furnishings, fire-fighting foams, surfactants, textiles, adhesives, waxes, polishes, and leather. 1 It was reported that the market size of fluorotelomers was 26.5 kt in 2015, and its annual growth rate is estimated to be 12.7%. 2 Among fluorotelomers, fluorotelomer alcohol (FTOH) products dominate global consumption; these products reportedly made up approximately 32% of the overall volume of fluorotemomers in 2013. 3 8:2 FTOH is the most abundant FTOH homologue and is ubiquitous in the environment. 4 Chen et al. 5 detected FTOHs in several wastewater treatment plants in China, and the study also found that 8:2 FTOH was the primary FTOH in the influent, secondary effluent, and sludge, with the concentrations ranging from 2.10 to 11.0 ng/L, 3.05 to 12.4 ng/L, and 0.36 to 1.91 ng/g dry weight, respectively. Bach et al. 6 assessed 14 perfluorinated compounds (PFCs) in water samples in France and found that the concentrations of 8:2 FTOH were 117 ng/L and 213 ng/L in tap and surface water, respectively. Additionally, 8:2 FTOH was commonly detected in food contact materials (FCMs). For example, 8:2 FTOH was detected in most Chinese and American FCM samples at concentra...

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Section: Discussionmentioning

confidence: 82%

8:2 Fluorotelomer alcohol causes immunotoxicity and liver injury in adult male C57BL/6 mice

Wang

Kong

et al. 2018

Environmental Toxicology

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“…Particularly, it is not yet clear if the zebrafish embryos are experiencing neutropenia from PFOA exposure resulting in a reduction in the number of circulating neutrophils (consistent with the systemic leukocytopenia reported in an earlier mouse study [ 20 ]), or a specific reduction in neutrophil chemotaxis at the wound site (supported by in vitro data [ 19 ] but not tested in vivo). Effects to neutrophil chemotaxis are supported by alteration of inflammatory cytokines and TLR-2 pathways (including MyD88 and NF-kB expression) seen in adult zebrafish exposed to 0.05, 0.1, 0.5, or 1 mg/L PFOA for 21 days [ 21 ]. In the current study, the overall neutrophil pool (as evidenced by average neutrophil numbers in the entire trunk and tail region) was similar across treatments which suggest that there is no reduction in overall neutrophil count between PFOA treatments.…”

Section: Discussionmentioning

confidence: 99%

Exposure to perfluorooctanoic acid (PFOA) decreases neutrophil migration response to injury in zebrafish embryos

et al. 2020

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Objective Perfluorooctanoic acid (PFOA) is a ubiquitous environmental contaminant and a known immune suppressant in humans and experimental animal models. Studies on PFOA have focused on suppression of the adaptive immune response; however, little is known of the impact on innate immunity, especially during embryogenesis. Therefore, we utilized the zebrafish chemotaxis assay coupled with in situ hybridization for myeloperoxidase expression to determine the effects of PFOA exposure on neutrophil migration in the developing zebrafish embryo. Zebrafish embryos are a well-established in vivo model that exhibit high homology with the development of human innate immunity. Results Treatment of zebrafish with increasing concentrations of PFOA identified the lethal concentration in 50% of the embryos (LC 50 ) to be 300 mg/L. Utilizing the zebrafish chemotaxis assay, this study showed that wounding induced significant neutrophil migration to the site of injury, and that neutrophil number in the wound region was significantly reduced in response to 48-h PFOA exposure (well below doses causing acute mortality). This study demonstrates that the developing embryo is sensitive to PFOA exposure and that PFOA can modify the innate immune system during embryonic development. These results lay the groundwork for future investigation on the mechanisms underlying PFOA-induced developmental immunotoxicity.

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“…Furthermore, an immune reaction with subsequent inflammation is considered a cornerstone in atherosclerosis development [ 28 ]. From that perspective, it is interesting that exposure to PFASs has been associated with a number of perturbations in the immune system in experimental studies [ 29 – 31 ]. Another recently highlighted mechanism of PFASs is that PFASs might influence circulating microparticles, being markers of endothelial dysfunction constituting an early step in atherosclerosis formation [ 23 ].…”

Section: Discussionmentioning

confidence: 99%

Changes in plasma levels of perfluoroalkyl substances (PFASs) are related to increase in carotid intima-media thickness over 10 years – a longitudinal study

et al. 2018

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BackgroundIt has previously been reported that the environmental contaminants perfluoroalkyl substances (PFASs) are linked to atherosclerosis in cross-sectional studies. Since cross-sectional studies could be subject to reverse causation, the purpose of this study was to analyze if the longitudinal changes in PFASs during a 10-year follow-up were related to the change in carotid artery intima-media thickness (IMT, ultrasound) during the same period.MethodsIn the Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS) study, 1016 individuals were investigated at age 70; 826 of them were reinvestigated at age 75 and 602 at age 80 years. Eight different PFASs were measured in plasma by ultra-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS), and IMT was measured at all three time points. Random-effects mixed regression models were used to examine the associations over time.ResultsIMT increased 0.058 mm during the 10-year period (p < 0.0001). Following adjustment for baseline values of PFASs (age 70) and sex, the changes in plasma levels of 6 of the 8 measured PFASs were significantly related to the change in IMT over the 10-year follow-up period in a positive fashion (p < 0.0062 using Bonferroni correction for 8 tests). Further adjustment for traditional cardiovascular (CV) risk factors (HDL and LDL cholesterol, smoking, systolic blood pressure, statin use, fasting glucose and serum triglycerides) affected these relationships only marginally.ConclusionThe change in plasma levels of several PFASs during 10 years was positively related to increase in IMT seen during the same period, giving prospective evidence that PFASs might interfere with the atherosclerotic process.

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The role of interleukin family in perfluorooctanoic acid (PFOA)-induced immunotoxicity

Cited by 39 publications

References 73 publications

8:2 Fluorotelomer alcohol causes immunotoxicity and liver injury in adult male C57BL/6 mice

8:2 Fluorotelomer alcohol causes immunotoxicity and liver injury in adult male C57BL/6 mice

Exposure to perfluorooctanoic acid (PFOA) decreases neutrophil migration response to injury in zebrafish embryos

Changes in plasma levels of perfluoroalkyl substances (PFASs) are related to increase in carotid intima-media thickness over 10 years – a longitudinal study

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