Altered Cytokine Production in Mice Exposed to Lead Acetate

Iavicoli, Ivo; Marinaccio, Alessandro; Castellino, N; Carelli, G

doi:10.1177/03946320040170s216

Cited by 13 publications

(5 citation statements)

References 27 publications

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“…Due to lead’s short half-life time in the blood, blood lead tests cannot be used to diagnose or rule out evidence of exposure that occurred more than six weeks before testing. Studies show that even low-level exposures to lead impair cell-mediated immunity by upsetting the balance between Th1- and Th2- like T lymphocytes, which alters cytokine expression [ 27 , 28 ].…”

Section: Resultsmentioning

confidence: 99%

DNA Damage, Cell Cycle Arrest, and Apoptosis Induction Caused by Lead in Human Leukemia Cells

Yedjou,

Tchounwou,

Tchounwou

2015

IJERPH

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In recent years, the industrial use of lead has been significantly reduced from paints and ceramic products, caulking, and pipe solder. Despite this progress, lead exposure continues to be a significant public health concern. The main goal of this research was to determine the in vitro mechanisms of lead nitrate [Pb(NO3)2] to induce DNA damage, apoptosis, and cell cycle arrest in human leukemia (HL-60) cells. To reach our goal, HL-60 cells were treated with different concentrations of Pb(NO3)2 for 24 h. Live cells and necrotic death cells were measured by the propidium idiode (PI) assay using the cellometer vision. Cell apoptosis was measured by the flow cytometry and DNA laddering. Cell cycle analysis was evaluated by the flow cytometry. The result of the PI demonstrated a significant (p < 0.05) increase of necrotic cell death in Pb(NO3)2-treated cells, indicative of membrane rupture by Pb(NO3)2 compared to the control. Data generated from the comet assay indicated a concentration-dependent increase in DNA damage, showing a significant increase (p < 0.05) in comet tail-length and percentages of DNA cleavage. Data generated from the flow cytometry assessment indicated that Pb(NO3)2 exposure significantly (p < 0.05) increased the proportion of caspase-3 positive cells (apoptotic cells) compared to the control. The flow cytometry assessment also indicated Pb(NO3)2 exposure caused cell cycle arrest at the G0/G1 checkpoint. The result of DNA laddering assay showed presence of DNA smear in the agarose gel with little presence of DNA fragments in the treated cells compared to the control. In summary, Pb(NO3)2 inhibits HL-60 cells proliferation by not only inducing DNA damage and cell cycle arrest at the G0/G1 checkpoint but also triggering the apoptosis through caspase-3 activation and nucleosomal DNA fragmentation accompanied by secondary necrosis. We believe that our study provides a new insight into the mechanisms of Pb(NO3)2 exposure and its associated adverse health effects.

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Section: Resultsmentioning

confidence: 99%

DNA Damage, Cell Cycle Arrest, and Apoptosis Induction Caused by Lead in Human Leukemia Cells

Yedjou,

Tchounwou,

Tchounwou

2015

IJERPH

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“…Exposure to lead has also been implicated in the modification of cytokine gene expression and production in mammals both in vivo and in vitro (Yucesoy et al 1997; Krocova et al 2000; Cheng et al 2002; Heo et al 2007). More specifically, Pb 2+ exposure was found to result in an imbalance between pro‐inflammatory, cell‐mediated T helper 1 (Th1) and anti‐inflammatory, humoral‐mediated T helper 2 (Th2) response by reducing Th1 cytokines (e.g., IFN‐γ and IL‐2) and enhancing Th2 cytokine (IL‐4) at the same time (Lawrence and McCabe 2002; Iavicoli et al 2004). Because the major targets of Th1 responses are cellular antigens including viruses and bacteria, whereas the major targets for Th2 responses are extracellular parasites (Degen et al 2005), the Pb 2+ ‐induced shifting to Th2 immunity could probably weaken the host defense of viruses in birds.…”

Section: Introductionmentioning

confidence: 99%

Modulatory Effects of Pb2+ on Virally Challenged Chicken Macrophage (HD-11) and B-Lymphocyte (DT40) Cell Lines In Vitro

Han

García-Mendoza

Berg

et al. 2020

Environmental Toxicology and Chemistry

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Elevated levels of lead have been found in waterfowl, due to human activities. Lead may cause immunomodulatory effects, but the mechanisms are largely unknown, especially after viral challenges. To characterize avian immunomodulatory hazards of lead (Pb)2+, we used chicken macrophage (HD‐11) and B‐lymphocyte (DT40) cell lines, as in vitro models for the innate and adaptive immune systems, respectively. The cells were activated via toll‐like receptor‐3 by polyinosinic–polycytidylic acid sodium salt (poly I:C), mimicking viral infections. Our results indicate that Pb2+ is cytotoxic to both cell lines, macrophages being more sensitive. De novo synthesis of glutathione plays an important role in protecting macrophages from Pb2+ intoxication, which might also be closely involved in the induction of nitric oxide after Pb2+ exposure. Stimulatory effects on cell proliferation were noticed at noncytotoxic Pb2+ concentrations as well. Exposure to Pb2+ could also affect the inflammatory status by inhibiting the pro‐inflammatory interferon (IFN)‐γ while promoting the production of anti‐inflammatory type I IFNs in both macrophages and B‐cells, and increasing intracellular IgM levels in B‐cells. These results suggest that the immunomodulatory effects of Pb2+ in birds are probably closely associated with disruption of immune cell proliferation and cytokine production, potentially causing disorders of the avian immune system. Environ Toxicol Chem 2020;39:1060–1070. © 2020 The Authors. Environmental Toxicology and Chemistry published by Wiley Periodicals LLC

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“…Both in vivo and in vitro experiments showed increased plasma IL-4 and IgE levels and a profound decrease of INF-γ and IL-2 production, indicating that Pb skews naïve T-cells toward Th2 (Heo et al 1996, 1997; Iavicoli et al 2004, 2006; Kasten-Jolly et al 2010). Moreover, Heo et al (1998) suggested that Pb inhibits Th1 development by increasing adenylate cyclase activity, and thereby increasing cyclic AMP levels.…”

Section: Discussionmentioning

confidence: 99%

Sub-Chronic Oral Exposure to Iridium (III) Chloride Hydrate in Female Wistar Rats: Distribution and Excretion of the Metal

et al. 2012

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Iridium tissue distribution and excretion in female Wistar rats following oral exposure to iridium (III) chloride hydrate in drinking water (from 1 to 1000 ng/ml) in a sub-chronic oral study were determined. Samples of urine, feces, blood and organs (kidneys, liver, lung, spleen and brain) were collected at the end of exposure. The most prominent fractions of iridium were retained in kidney and spleen; smaller amounts were found in lungs, liver and brain. Iridium brain levels were lower than those observed in other tissues but this finding can support the hypothesis of iridium capability to cross the blood brain barrier. The iridium kidney levels rose significantly with the administered dose. At the highest dose, important amounts of the metal were found in serum, urine and feces. Iridium was predominantly excreted via feces with a significant linear correlation with the ingested dose, which is likely due to low intestinal absorption of the metal. However, at the higher doses iridium was also eliminated through urine. These findings may be useful to help in the understanding of the adverse health effects, particularly on the immune system, of iridium dispersed in the environment as well as in identifying appropriate biological indices of iridium exposure.

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Altered Cytokine Production in Mice Exposed to Lead Acetate

Cited by 13 publications

References 27 publications

DNA Damage, Cell Cycle Arrest, and Apoptosis Induction Caused by Lead in Human Leukemia Cells

DNA Damage, Cell Cycle Arrest, and Apoptosis Induction Caused by Lead in Human Leukemia Cells

Modulatory Effects of Pb2+ on Virally Challenged Chicken Macrophage (HD-11) and B-Lymphocyte (DT40) Cell Lines In Vitro

Sub-Chronic Oral Exposure to Iridium (III) Chloride Hydrate in Female Wistar Rats: Distribution and Excretion of the Metal

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