Cytokine Regulation of a Rodent Model of Mercuric Chloride-Induced Autoimmunity

Bagenstose, Lee M.; Salgame, Padmini; Monestier, Marc

doi:10.2307/3434344

Cited by 7 publications

(7 citation statements)

References 36 publications

(44 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…According to literary data, the close relation between accumulation of immune complexes in tissues and hypercholesterolemia is the characteristic feature of the murine lupus-like syndromes developing spontaneously in (NZB x NZW)F1 mice, in MRL/lpr, BXSB and other relevant mouse strains (Ogura et al, 1989;Itoh et al, 1994;Gu et al, 1999;Kono et al, 2000;Lawman et al, 2004). Similar association has come to light also in experimental investigations of a various immune complex renal injuries induced in animals by the administration of HgCl 2 , cationic bovine serum albumin and antibodies to renal proteins (Couser et al, 1978;Bagenstose et al, 1999;Shi et al, 2005;Wu et al, 2008). Described in this paper (see Table 5) increase of TNF in the serum of lupus mice emerging simultaneously with the appearance of proteinuria and hypercholesterolemia, also can be attributed to decreased production of 27-hydroxycholesterol since oxysterols (via LXR) inhibit an expression and synthesis of proinflammatory cytokines (Dushkin et al, 1998;Hong et al, 2011).…”

Section: Change Of Cholesterol Metabolism In Recipients With Glomerulmentioning

confidence: 76%

The Experimental Model of the Autoimmune Glomerulonephritis Induced by the Chronic Graft versus Host Reaction

Kudaeva¹,

Колесникова²,

Гойман³

et al. 2011

An Update on Glomerulopathies - Etiology and Pathogenesis

View full text Add to dashboard Cite

Section: Change Of Cholesterol Metabolism In Recipients With Glomerulmentioning

confidence: 76%

The Experimental Model of the Autoimmune Glomerulonephritis Induced by the Chronic Graft versus Host Reaction

Kudaeva¹,

Колесникова²,

Гойман³

et al. 2011

An Update on Glomerulopathies - Etiology and Pathogenesis

View full text Add to dashboard Cite

“…This disorder is characterized by autoantibody production, increases in serum Igs, including IgE, polyclonal activation of B and T lymphocytes, and renal immune complex deposition, resulting in glomerulonephritis [9 -12]. Metal-induced autoimmunity in mice shares many similarities with the corresponding disorder in BN rats, including the production of autoantibodies [6]. The main target of the autoantibodies is fibrillarin, a 34-kDa ribonucleoprotein.…”

Section: Introductionmentioning

confidence: 98%

“…Several rodent models exist for Hg (II)-, Au (III)-, and Ag (I)-induced autoimmunity [1][2][3][4][5][6][7]. Among these ions, Hg (II) is the best known to evoke autoimmunity in genetically susceptible animal models.…”

Section: Introductionmentioning

confidence: 99%

Ca2+-dependent mast cell death induced by Ag (I) via cardiolipin oxidation and ATP depletion

Inoue

Suzuki

Yoshimaru

et al. 2009

Journal of Leukocyte Biology

View full text Add to dashboard Cite

In genetically susceptible humans and/or experimental animals, ions of heavy metals, Hg (II), Au (III), and Ag (I) have been shown to strongly induce autoimmunity, in which mast cells have been implicated to play a role. Here, we demonstrate that Ag (I) application results in mast cell death through a unique Ca(2+)- and mitochondria-dependent pathway. As cellular susceptibilities to Ag (I) cytotoxicity varied considerably, we analyzed the cell death pathway in the low and high responding cells. In the low responding cells, long application (e.g., 20 h) of Ag (I) at concentrations (>or=30 microM) induced cell death, which was accompanied by mitochondrial membrane depolarization, cyt c release, and caspase-3/7 activation but was not prevented by selective inhibitors of caspase-3/7 and the mitochondrial permeability transition. The cell death was preceded by elevations in the cytoplasmic and mitochondrial Ca(2+) levels, and Ca(2+) responses and cell death were prevented by thiol reagents, including DTT, N-acetylcysteine, and reduced glutathione monoethyl ester. In the high responding cells, Ag (I) evoked considerable cell death by necrosis within 1 h, without inducing caspase activation, and this cell death was reduced significantly by depleting extracellular but not intracellular Ca(2+). Moreover, Ag (I) strongly induced Ca(2+)-dependent CL oxidation and intracellular ATP depletion, both of which were blocked by thiol reagents. These results suggest that Ag (I) activates thiol-dependent Ca(2+) channels, thereby promoting Ca(2+)-dependent CL oxidation, cyt c release, and ATP depletion. This necrotic cell death may play roles in Ag-induced inflammation and autoimmune disorders.

show abstract

“…Exposure to subtoxic doses of mercury leads to a Th2 deviation in most mouse strains [36][37][38][39][40][41][42], which is a robust way of influencing the Th1/Th2 balance [43]. This model has been used previously to assess the importance of the Th1/ Th2 balance in murine infections [44].…”

Section: Introductionmentioning

confidence: 99%

Mercury exposure as a model for deviation of cytokine responses in experimental Lyme arthritis: HgCl2 treatment decreases T helper cell type 1-like responses and arthritis severity but delays eradication of Borrelia burgdorferi in C3H/HeN mice

Ekerfelt

Andersson

Olausson

et al. 2007

Clinical and Experimental Immunology

View full text Add to dashboard Cite

SummaryLyme borreliosis is a complex infection, where some individuals develop so-called 'chronic borreliosis'. The pathogenetic mechanisms are unknown, but the type of immune response is probably important for healing. A strong T helper cell type 1 (Th1)-like response has been suggested as crucial for eradication of Borrelia and for avoiding development of chronic disease. Many studies aimed at altering the Th1/Th2 balance in Lyme arthritis employed mice deficient in cytokine genes, but the outcome has not been clear-cut, due possibly to the high redundancy of cytokines. This study aimed at studying the importance of the Th1/Th2 balance in murine Borrelia arthritis by using the Th2-deviating effect of subtoxic doses of inorganic mercury. Ninety-eight C3H/HeN mice were divided into four groups: Borrelia-infected (Bb), Borrelia-infected exposed to HgCl2 (BbHg), controls exposed to HgCl2 alone and normal controls. Mice were killed on days 3, 16, 44 and 65 post-Borrelia inoculation. Arthritis severity was evaluated by histology, spirochaetal load determined by Borrelia culture, IgG2a-and IgE-levels analysed by enzymelinked immunosorbemt assay (ELISA) and cytokine-secreting cells detected by enzyme-linked immunospot (ELISPOT). BbHg mice showed less severe histological arthritis, but delayed eradication of spirochaetes compared to Bb mice, associated with increased levels of IgE (Th2-induced) and decreased levels of IgG2a (Th1-induced), consistent with a Th2-deviation. Both the numbers of Th1 and Th2 cytokine-secreting cells were reduced in BbHg mice, possibly explained by the fact that numbers of cytokine-secreting cells do not correlate with cytokine concentration. In conclusion, this study supports the hypothesis that a Th1-like response is required for optimal eradication of Borrelia.

show abstract

Cytokine Regulation of a Rodent Model of Mercuric Chloride-Induced Autoimmunity

Cited by 7 publications

References 36 publications

The Experimental Model of the Autoimmune Glomerulonephritis Induced by the Chronic Graft versus Host Reaction

The Experimental Model of the Autoimmune Glomerulonephritis Induced by the Chronic Graft versus Host Reaction

Ca2+-dependent mast cell death induced by Ag (I) via cardiolipin oxidation and ATP depletion

Mercury exposure as a model for deviation of cytokine responses in experimental Lyme arthritis: HgCl2 treatment decreases T helper cell type 1-like responses and arthritis severity but delays eradication of Borrelia burgdorferi in C3H/HeN mice

Contact Info

Product

Resources

About