Author | Francischetti, Ivo M. B | |
Author | Gordon, Emile | |
Author | Bizzarro, Bruna | |
Author | Gera, Nidhi | |
Author | Andrade, Bruno de Bezerril | |
Author | Oliveira, Fabiano | |
Author | Ma, Dongying | |
Author | Assumpção, Teresa Cristina França | |
Author | Ribeiro, José M. C | |
Author | Pena, Mirna | |
Author | Qi, Chen-Feng | |
Author | Diouf, Ababacar | |
Author | Moretz, Samuel E | |
Author | Long, Carole A | |
Author | Ackerman, Hans C | |
Author | Pierce, Susan K | |
Author | Nunes, Anderson Sá | |
Author | Waisberg, Michael | |
Access date | 2018-02-22T13:29:59Z | |
Available date | 2018-02-22T13:29:59Z | |
Document date | 2014 | |
Citation | FRANCISCHETTI, I. M. B. et al. Tempol, an intracellular antioxidant, inhibits tissue factor expression, attenuates dendritic cell function, and is partially protective in a murine model of cerebral malaria. PLoS One, v. 9, n. 2, e87140, 2014. | pt_BR |
ISSN | 1932-6203 | pt_BR |
URI | https://www.arca.fiocruz.br/handle/icict/24911 | |
Description | ANDRADE, Bruno Bezerril. “Documento produzido em parceria ou por autor vinculado à Fiocruz, mas não consta à informação no documento”. | pt_BR |
Sponsorship | Research Program of the Division of Intramural Research, National Institute of Allergy and Infectious
Diseases, National Institutes of Health. | pt_BR |
Language | eng | pt_BR |
Publisher | Public Library of Science | pt_BR |
Rights | open access | pt_BR |
Subject in Portuguese | Malaria cerebral | pt_BR |
Subject in Portuguese | Células dendríticas | pt_BR |
Subject in Portuguese | Reação em cadeia da polimerase em tempo real | pt_BR |
Subject in Portuguese | Antioxidantes | pt_BR |
Subject in Portuguese | Plasmodium Falciparum | pt_BR |
Title | Tempol, an intracellular antioxidant, inhibits tissue factor expression, attenuates dendritic cell function, and is partially protective in a murine model of cerebral malaria | pt_BR |
Type | Article | pt_BR |
DOI | 10.1371/journal.pone.0087140 | |
Abstract | The role of intracellular radical oxygen species (ROS) in pathogenesis of cerebral malaria (CM) remains incompletely understood. Methods and Findings: We undertook testing Tempol—a superoxide dismutase (SOD) mimetic and pleiotropic intracellular
antioxidant—in cells relevant to malaria pathogenesis in the context of coagulation and inflammation. Tempol was also
tested in a murine model of CM induced by Plasmodium berghei Anka infection. Tempol was found to prevent transcription
and functional expression of procoagulant tissue factor in endothelial cells (ECs) stimulated by lipopolysaccharide (LPS). This
effect was accompanied by inhibition of IL-6, IL-8, and monocyte chemoattractant protein (MCP-1) production. Tempol also
attenuated platelet aggregation and human promyelocytic leukemia HL60 cells oxidative burst. In dendritic cells, Tempol
inhibited LPS-induced production of TNF-a, IL-6, and IL-12p70, downregulated expression of co-stimulatory molecules, and
prevented antigen-dependent lymphocyte proliferation. Notably, Tempol (20 mg/kg) partially increased the survival of mice
with CM. Mechanistically, treated mice had lowered plasma levels of MCP-1, suggesting that Tempol downmodulates EC
function and vascular inflammation. Tempol also diminished blood brain barrier permeability associated with CM when
started at day 4 post infection but not at day 1, suggesting that ROS production is tightly regulated. Other antioxidants—
such as a-phenyl N-tertiary-butyl nitrone (PBN; a spin trap), MnTe-2-PyP and MnTBAP (Mn-phorphyrin), Mitoquinone (MitoQ)
and Mitotempo (mitochondrial antioxidants), M30 (an iron chelator), and epigallocatechin gallate (EGCG; polyphenol from
green tea) did not improve survival. By contrast, these compounds (except PBN) inhibited Plasmodium falciparum growth in
culture with different IC50s. Knockout mice for SOD1 or phagocyte nicotinamide adenine dinucleotide phosphate (NADPH)
oxidase (gp91phox–/–) or mice treated with inhibitors of SOD (diethyldithiocarbamate) or NADPH oxidase (diphenyleneiodonium)
did not show protection or exacerbation for CM.
Conclusion: Results with Tempol suggest that intracellular ROS contribute, in part, to CM pathogenesis. Therapeutic
targeting of intracellular ROS in CM is discussed. | pt_BR |
Affilliation | National Institutes of Health. National Institute of Allergy and Infectious Diseases. Laboratory of Malaria and Vector Research. Rockville, MD, USA | pt_BR |
Affilliation | National Institutes of Health. National Institute of Allergy and Infectious Diseases. Laboratory of Immunogenetics. Rockville, MD, USA | pt_BR |
Affilliation | University of São Paulo. Institute of Biomedical Sciences. Laboratory of Experimental Immunology. Department of Immunology. São Paulo, SP, Brazil | pt_BR |
Affilliation | National Institutes of Health. National Institute of Allergy and Infectious Diseases. Laboratory of Immunogenetics. Rockville, MD, USA | pt_BR |
Affilliation | National Institute of Allergy and Infectious Diseases. Laboratory of Parasitic Diseases. Bethesda, MD, USA | pt_BR |
Affilliation | National Institutes of Health. National Institute of Allergy and Infectious Diseases. Laboratory of Malaria and Vector Research. Rockville, MD, USA | pt_BR |
Affilliation | National Institutes of Health. National Institute of Allergy and Infectious Diseases. Laboratory of Malaria and Vector Research. Rockville, MD, USA | pt_BR |
Affilliation | National Institutes of Health. National Institute of Allergy and Infectious Diseases. Laboratory of Malaria and Vector Research. Rockville, MD, USA | pt_BR |
Affilliation | National Institutes of Health. National Institute of Allergy and Infectious Diseases. Laboratory of Malaria and Vector Research. Rockville, MD, USA | pt_BR |
Affilliation | National Institutes of Health. National Institute of Allergy and Infectious Diseases. Laboratory of Immunogenetics. Rockville, MD, USA | pt_BR |
Affilliation | National Institutes of Health. National Institute of Allergy and Infectious Diseases. Laboratory of Immunogenetics. Rockville, MD, USA | pt_BR |
Affilliation | National Institutes of Health. National Institute of Allergy and Infectious Diseases. Laboratory of Malaria and Vector Research. Rockville, MD, USA | pt_BR |
Affilliation | National Institutes of Health. National Institute of Allergy and Infectious Diseases. Laboratory of Malaria and Vector Research. Rockville, MD, USA | pt_BR |
Affilliation | National Institutes of Health. National Institute of Allergy and Infectious Diseases. Laboratory of Malaria and Vector Research. Rockville, MD, USA | pt_BR |
Affilliation | National Institutes of Health. National Institute of Allergy and Infectious Diseases. Laboratory of Malaria and Vector Research. Rockville, MD, USA | pt_BR |
Affilliation | National Institutes of Health. National Institute of Allergy and Infectious Diseases. Laboratory of Immunogenetics. Rockville, MD, USA | pt_BR |
Affilliation | University of São Paulo. Institute of Biomedical Sciences. Laboratory of Experimental Immunology. Department of Immunology. São Paulo, SP, Brazil | pt_BR |
Affilliation | National Institutes of Health. National Institute of Allergy and Infectious Diseases. Laboratory of Immunogenetics. Rockville, MD, USA / University of Virginia. Department of Pathology. Charlottesville, Virginia, USA | pt_BR |
Subject | Malaria cerebral | pt_BR |
Subject | Dendritic Cells | pt_BR |
Subject | Real-Time Polymerase Chain Reaction | pt_BR |
Subject | Antioxidants | pt_BR |
Subject | Plasmodium Falciparum | pt_BR |