Metals and Kidney Autoimmunity

Bigazzi, Pierluigi E.

doi:10.2307/3434338

Cited by 14 publications

(10 citation statements)

References 52 publications

(65 reference statements)

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“…Although Hg is known to induce toxic effects in different body organs and cellular components including renal proximal tubules and jejunal epithelial cells (Lash and Zalups, 1992;Pritchard, 1979;Bigazzi, 1999), non-existing data is available regarding the effect of Hg on renal or jejunal AADC activity. The results of the present study in HgCl 2 -treated rats showing a reduced renal AADC activity with no changes in jejunal AADC activity suggest that the decrease in enzyme activity in the renal parenchyma may result from Hg-independent mechanisms and further agree with the observations suggesting that the main controlling factors for renal dopamine production are related to the local delivery of sodium as well as the intracellular electrolyte and hormonal medium (Lee, 1993).…”

Section: Discussionmentioning

confidence: 98%

Blunted renal dopaminergic system activity in HgCl2-induced membranous nephropathy

2006

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Section: Discussionmentioning

confidence: 98%

Blunted renal dopaminergic system activity in HgCl2-induced membranous nephropathy

2006

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“…Cases of mercury-induced autoimmune kidney disease mediated by immune complex deposition have been noted historically in highly exposed populations, though there is some debate as to the role of autoimmunity in these cases given that mercury also causes direct damage to the kidneys (Barr et al, 1973; Bigazzi, 1999; Cardenas et al, 1993; Tubbs et al, 1982). Several studies, using levels of circulating anti-laminin antibodies and immune complex as a marker for disease, failed to find a correlation between occupational mercury exposure and markers of immune dysfunction (Barregard et al, 1997; Bernard et al, 1987; Ellingsen et al, 2000; Langworth et al, 1992).…”

Section: Introductionmentioning

confidence: 99%

Mercury exposure, serum antinuclear/antinucleolar antibodies, and serum cytokine levels in mining populations in Amazonian Brazil: A cross-sectional study

Gardner

Nyland

Silva

et al. 2010

Environmental Research

151

119

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Mercury is an immunotoxic substance that has been shown to induce autoimmune disease in rodent models, characterized by lymphoproliferation, overproduction of immunoglobulin (IgG and IgE), and high circulating levels of autoantibodies directed at antigens located in the nucleus (anti-nuclear autoantibodies, or ANA) or the nucleolus (anti-nucleolar autoantibodies, or ANoA). We have reported elevated levels of ANA and ANoA in human populations exposed to mercury in artisanal gold mining, though other confounding variables that may also modulate ANA/ANoA levels were not well-controlled. The goal of this study is to specifically test whether occupational and environmental conditions (other than mercury exposure) that are associated with artisanal gold mining affect the prevalence of markers of autoimmune dysfunction. We measured ANA, ANoA, and cytokine concentrations in serum and compared results from mercury-exposed artisanal gold miners to those from diamond and emerald miners working under similar conditions and with similar socioeconomic status and risks of infectious disease. Mercury-exposed gold miners had higher prevalence of detectable ANA and ANoA and higher titers of ANA and ANoA as compared to diamond and emerald miners with no occupational mercury exposure. Also, mercury-exposed gold-miners with detectable ANA or ANoA in serum had significantly higher concentrations of pro-inflammatory cytokines IL-1β, TNF-α, and IFN-γ in serum as compared to the diamond and emerald miners. This study provides further evidence that mercury exposure may lead to autoimmune dysfunction and systemic inflammation in affected populations.

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“…Environmental or occupational exposures to metal compounds including mercurials have been linked to dysfunctions of the immune system, such as allergic and autoimmune diseases [1, 2, 3, 4]. Mercuric compounds induce abnormal immune responses including induction of specific and polyclonal IgE [5]and autoimmunity [6, 7]in rats and mice.…”

Section: Introductionmentioning

confidence: 99%

c-Jun N-Terminal Kinase Is Involved in Mercuric Ions-Mediated Interleukin-4 Secretion in Mast Cells

Walczak‐Drzewiecka¹,

Wyczółkowska²,

Dastych³

2005

Int Arch Allergy Immunol

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Background: Interleukin (IL)-4 plays a prominent role in immune response. Mercuric compounds upregulate IL-4 expression in animal tissues, and this upregulation plays a role in mercuric-mediated immunomodulation. Mercuric ions-mediated IL-4 expression was observed in vitro in T lymphocytes and mast cells. In the present study, we investigated molecular mechanisms responsible for this effect of mercuric ions in mast cells. Methods: C1.MC/C57.1 mouse mast cells were exposed in vitro to increasing concentrations of Hg²⁺ in the absence or presence of the specific c-Jun N-terminal kinase (JNK) inhibitor SP600125. The level of phosphorylated c-Jun in mast cells was determined by Western blotting, JNK activity assessed with in vitro kinase assay and the amount of secreted IL-4 determined by ELISA. Results: We observed that Hg²⁺ upregulated c-Jun phosphorylation on Ser 73 at concentrations which overlapped concentrations mediating IL-4 secretion. Phosphorylation of c-Jun in mast cells was associated with an increase in JNK activity. The specific JNK inhibitor SP600125 abolished both mercuric-induced c-Jun phosphorylation and IL-4 secretion in mast cells. Conclusions: These observations are consistent with the hypothesis that JNK is one of the signaling proteins mediating the effect of Hg²⁺ on IL-4 expression in mast cells and is engaged in environmentally mediated immunomodulation.

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Metals and Kidney Autoimmunity

Cited by 14 publications

References 52 publications

Blunted renal dopaminergic system activity in HgCl2-induced membranous nephropathy

Blunted renal dopaminergic system activity in HgCl2-induced membranous nephropathy

Mercury exposure, serum antinuclear/antinucleolar antibodies, and serum cytokine levels in mining populations in Amazonian Brazil: A cross-sectional study

c-Jun N-Terminal Kinase Is Involved in Mercuric Ions-Mediated Interleukin-4 Secretion in Mast Cells

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