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  • anthrax lethal toxin  (3)
  • Cell & Developmental Biology  (2)
  • 1
    ISSN: 1573-6822
    Keywords: anthrax lethal toxin ; cytokine ; dehydroepiandrosterone ; melatonin ; tumor necrosis factor α
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract The lethal toxin of Bacillus anthracis, which is composed of two separate proteinaceous exotoxins, namely protective antigen and lethal factor, is central to the pathogenesis of anthrax. Low levels of this toxin are known to induce release of cytokines such as tumor necrosis factor α (TNF-α). In the present study we investigated the effect of dehydroepiandrosterone (DHEA), melatonin (MLT), or DHEA + MLT on production of lethal toxin-induced TNF-α in mouse peritoneal macrophages. We found that treatment with DHEA significantly inhibited the TNF-α production caused by anthrax lethal toxin. Exposure of MLT to anthrax lethal toxin-treated macrophages also decreased the release of TNF-α to the extracellular medium as compared to the control. However, combined use of DHEA and MLT also inhibited TNF-α release, but not more than single therapies. These results suggest that DHEA and MLT may have a therapeutic role in reducing the increased cytokine production induced by anthrax lethal toxin.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1573-6822
    Keywords: anthrax lethal toxin ; cytotoxicity ; intracellular calcium antagonist ; macrophage
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract The lethal toxin ofBacillus anthracis is central to the pathogenesis of anthrax. Using primary cultures of mouse peritoneal macrophages, we have demonstrated that intracellular calcium release inhibitors protect against anthrax lethal toxin-induced cytotoxicity. The cytolytic effect of anthrax lethal toxin was markedly reduced by dantrolene, an inhibitor of calcium release from intracellular calcium stores. Pretreatment of macrophages with cyclosporin A, which has been shown to be a potent inhibitor of calcium release from mitochondria, also protected cells against cytotoxicity. These results indicate that calcium release from intracellular store may be an essential step for the propagation of anthrax lethal toxin-induced cell damage in macrophages. Thus our findings suggest that dantrolene, cyclosporin A, and possibly other drugs affecting intracellular calcium pools might be effectively preventing the toxicity from anthrax lethal toxin.
    Type of Medium: Electronic Resource
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  • 3
    Electronic Resource
    Electronic Resource
    Springer
    Cell biology and toxicology 15 (1999), S. 19-29 
    ISSN: 1573-6822
    Keywords: anthrax lethal toxin ; cytotoxicity ; macrophage ; phospholipase A2 ; protein kinase
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract The molecular mechanism of cytotoxic effect exerted by the lethal toxin (LeTx) of Bacillus anthracis is not well understood. In the present study, using primary culture of mouse peritoneal macrophages, we have investigated possible cytotoxic mechanisms. LeTx was not found to induce high levels of nitric oxide (NO) production for NO-mediated toxicity. Fragmentation of DNA, a biochemical marker of apoptosis, was not observed in LeTx-treated cells. Pretreatment of cells with antioxidants such as melatonin and dehydroepiandrosterone (DHEA) did not protect the LeTx-induced cytotoxicity. However, addition of phospholipase A2 (PLA2) inhibitors (quinacrine, p-bromophenacyl bromide, manoalide, butacaine) to the culture medium resulted in the inhibition of cytotoxicity of LeTx in a dose-dependent manner. LeTx-induced cytotoxicity was also inhibited by the tyrosine-specific protein kinase inhibitor genistein, but not by the protein kinase C inhibitors staurosporine or H-7. The results of these studies indicate a role for PLA2 and protein kinase in the cytotoxic mechanism of macrophages by anthrax lethal toxin.
    Type of Medium: Electronic Resource
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  • 4
    Electronic Resource
    Electronic Resource
    New York, NY [u.a.] : Wiley-Blackwell
    The @Anatomical Record 212 (1985), S. 250-254 
    ISSN: 0003-276X
    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine
    Notes: Autoradiographic and biochemical studies were used to demonstrate 1,25 (OH)2 vitamin D3 target cells in teeth. Incisor pulp of rats and molar pulp of humans were incubated in vitro with 3H-1,25 (OH)2 vitamin D3. Subsequent frozen-section autoradiography revealed a large population of cells in the pulp of both incisors and molars which selectively concentrated radioactivity in their nuclei. Extracts of incisor pulp from mature rats were found to bind 3H-1,25 (OH)2 vitamin D3 and this binding was displaceable with excess 1,25 (OH)2 vitamin D3. Sucrose density analysis revealed that the protein in tooth pulp which binds 1,25 (OH)2 vitamin D3 sediments at 3.2-3.5S. The 1,25 (OH)2 vitamin D3 receptor of intestine and kidney also sediments in this region, indicating that the 1,25 (OH)2 vitamin D3 binding protein of tooth pulp is similar to that found in other target organs. These autoradiographic and biochemical data indicate that pulpal cells of mature rat and human teeth contain receptors for 1,25 (OH)2 vitamin D3.
    Additional Material: 5 Ill.
    Type of Medium: Electronic Resource
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  • 5
    Electronic Resource
    Electronic Resource
    New York, NY [u.a.] : Wiley-Blackwell
    The @Anatomical Record 212 (1985), S. 301-306 
    ISSN: 0003-276X
    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine
    Notes: Target cells for 1,25(OH)2 vitamin D3 metabolites are identified in developing rodent teeth by the use of thaw-mount autoradiography. Following the injection of [26, 27-3H]-1,25(OH)2 vitamin D3 into 18-day- and 20-day-old fetal rats and neonatal mice, nuclear concentration of radioactivity is found in different cell types. In incisors of both animal groups, strong nuclear labeling is present predominantly in pulp cells, while relatively weakly labeled cells are found in the layers of odontoblasts, ameloblasts, and stratum intermedium. In molars, nuclear labeling is absent in fetal rats, but is present in 2-day-old neonates in pulp cells and cells in the layers of stratum intermedium of the first molars, but not in the second molars. The absence of labeled pulp cells in the progenitor regions of incisors and in molars of 20-day-old fetal rats, and differential ontogenic appearance of labeled pulp cells in molars, indicates that there is a critical period of receptor emergence. The finding that labeled pulp cells exist in the regions of incisors and molars where secretory odontoblasts are present suggests that nuclear uptake of 1,25(OH)2 vitamin D3 is related to cell maturation and differentiation, and topographically related to the formation of dentin. The results further suggest that, in contrast to bone, the predominant effect of 1,25(OH)2 vitamin D3 is not on tooth cells which are directly involved in the formation of calcified tissue, i.e., ameloblasts and odontoblasts, but rather on supporting tissues such as pulp cells and stratum intermedium.
    Additional Material: 12 Ill.
    Type of Medium: Electronic Resource
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