| Involvement of inflammatory chemokines in survival of human monocytes fed with malarial pigment. | |
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MedLine Citation:
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PMID: 20732999 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Hemozoin (HZ)-fed monocytes are exposed to strong oxidative stress, releasing large amounts of peroxidation derivatives with subsequent impairment of numerous functions and overproduction of proinflammatory cytokines. However, the histopathology at autopsy of tissues from patients with severe malaria showed abundant HZ in Kupffer cells and other tissue macrophages, suggesting that functional impairment and cytokine production are not accompanied by cell death. The aim of the present study was to clarify the role of HZ in cell survival, focusing on the qualitative and temporal expression patterns of proinflammatory and antiapoptotic molecules. Immunocytochemical and flow cytometric analyses showed that the long-term viability of human monocytes was unaffected by HZ. Short-term analysis by macroarray of a complete panel of cytokines and real-time reverse transcription (RT)-PCR experiments showed that HZ immediately induced interleukin-1β (IL-1β) gene expression, followed by transcription of eight additional chemokines (IL-8, epithelial cell-derived neutrophil-activating peptide 78 [ENA-78], growth-regulated oncogene α [GROα], GROβ, GROγ, macrophage inflammatory protein 1α [MIP-1α], MIP-1β, and monocyte chemoattractant protein 1 [MCP-1]), two cytokines (tumor necrosis factor alpha [TNF-α] and IL-1receptor antagonist [IL-1RA]), and the cytokine/chemokine-related proteolytic enzyme matrix metalloproteinase 9 (MMP-9). Furthermore, real-time RT-PCR showed that 15-HETE, a potent lipoperoxidation derivative generated by HZ through heme catalysis, recapitulated the effects of HZ on the expression of four of the chemokines. Intermediate-term investigation by Western blotting showed that HZ increased expression of HSP27, a chemokine-related protein with antiapoptotic properties. Taken together, the present data suggest that apoptosis of HZ-fed monocytes is prevented through a cascade involving 15-HETE-mediated upregulation of IL-1β transcription, rapidly sustained by chemokine, TNF-α, MMP-9, and IL-1RA transcription and upregulation of HSP27 protein expression. |
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Authors:
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Giuliana Giribaldi; Mauro Prato; Daniela Ulliers; Valentina Gallo; Evelin Schwarzer; Oskar B Akide-Ndunge; Elena Valente; Silvia Saviozzi; Raffaele A Calogero; Paolo Arese |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2010-08-23 |
Journal Detail:
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Title: Infection and immunity Volume: 78 ISSN: 1098-5522 ISO Abbreviation: Infect. Immun. Publication Date: 2010 Nov |
Date Detail:
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Created Date: 2010-10-19 Completed Date: 2010-11-12 Revised Date: 2011-07-28 |
Medline Journal Info:
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Nlm Unique ID: 0246127 Medline TA: Infect Immun Country: United States |
Other Details:
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Languages: eng Pagination: 4912-21 Citation Subset: IM |
Affiliation:
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Department of Genetics, Biology and Biochemistry, University of Torino Medical School, Turin, Italy. giuliana.giribaldi@unito.it |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Apoptosis / drug effects Cell Survival / drug effects Chemokines / genetics, immunology, metabolism* Flow Cytometry HSP27 Heat-Shock Proteins / genetics, metabolism Hemeproteins / pharmacology* Humans Hydroxyeicosatetraenoic Acids / metabolism Immunohistochemistry Inflammation / immunology, metabolism Interleukin-1beta / genetics, immunology Monocytes / drug effects*, immunology, physiology* Pigments, Biological / pharmacology* Plasmodium falciparum / metabolism Up-Regulation |
| Chemical | |
Reg. No./Substance:
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0/Chemokines; 0/HSP27 Heat-Shock Proteins; 0/HSPB1 protein, human; 0/Hemeproteins; 0/Hydroxyeicosatetraenoic Acids; 0/Interleukin-1beta; 0/Pigments, Biological; 39404-00-7/hemozoin; 73945-47-8/15-hydroxy-5,8,11,13-eicosatetraenoic acid |
| Comments/Corrections | |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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