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

Abstract

Experimental models of chemically induced autoimmunity have contributed to our understanding of the development of autoimmune diseases in humans. Heavy metals such as mercury induce a dramatic activation of the immune system and autoantibody production in genetically susceptible rats and mice. This autoimmune syndrome is dependent on T cells, which are important for B-Cell activation and cytokine secretion. Several studies have focused on the roles of T-helper (Th)1 and Th2 cells and their respective cytokines in the pathogenesis of mercury-induced disease. This article reviews recent studies that have examined the patterns of cytokine gene expression and where investigators have manipulated the Thl and Th2 responses that occur during mercury-induced autoimmunity. Finally, we will discuss some biochemical/molecular mechanisms by which heavy metals may induce cytokine gene expression.

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

“…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).…”

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

“…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.…”

“…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.…”

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

“…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].…”