| Plasmodium yoelii sporozoites modulate cytokine profile and induce apoptosis in murine Kupffer cells. | |
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MedLine Citation:
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PMID: 18656478 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Plasmodium sporozoites traverse Kupffer cells on their way into the liver. Sporozoite contact does not elicit a respiratory burst in these hepatic macrophages and blocks the formation of reactive oxygen species in response to secondary stimuli via elevation of the intracellular cAMP concentration. Here we show that increasing the cAMP level with dibutyryl cyclic adenosine monophosphate (db-cAMP) or isobutylmethylxanthine (IBMX) also modulates cytokine secretion in murine Kupffer cells towards an overall anti-inflammatory profile. Stimulation of Plasmodium yoelii sporozoite-exposed Kupffer cells with lipopolysaccharide or IFN-gamma reveals down-modulation of TNF-alpha, IL-6 and MCP-1, and up-regulation of IL-10. Prerequisite for this shift of the cytokine profile are parasite viability and contact with Kupffer cells, but not invasion. Whilst sporozoite-exposed Kupffer cells become TUNEL-positive and exhibit other signs of apoptotic death such as membrane blebbing, nuclear condensation and fragmentation, sporozoites remain intact and appear to transform to early exo-erythrocytic forms in Kupffer cell cultures. Together, the in vitro data indicate that Plasmodium possesses mechanisms to render Kupffer cells insensitive to pro-inflammatory stimuli and eventually eliminates these macrophages by forcing them into programmed cell death. |
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Authors:
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Christian Klotz; Ute Frevert |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't Date: 2008-07-09 |
Journal Detail:
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Title: International journal for parasitology Volume: 38 ISSN: 1879-0135 ISO Abbreviation: Int. J. Parasitol. Publication Date: 2008 Dec |
Date Detail:
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Created Date: 2008-11-10 Completed Date: 2009-08-05 Revised Date: 2011-09-26 |
Medline Journal Info:
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Nlm Unique ID: 0314024 Medline TA: Int J Parasitol Country: England |
Other Details:
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Languages: eng Pagination: 1639-50 Citation Subset: IM |
Affiliation:
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Department of Medical Parasitology, New York University School of Medicine, 341 E 25 Street, New York, NY 10010, USA. Christian.Klotz@staff.hu-berlin.de |
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| MeSH Terms | |
Descriptor/Qualifier:
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1-Methyl-3-isobutylxanthine
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metabolism Animals Apoptosis / immunology* Bucladesine / metabolism Cytokines / metabolism* Host-Parasite Interactions Interferon-gamma / pharmacology Interleukins / metabolism Kupffer Cells / drug effects, immunology* Lipopolysaccharides / pharmacology Liver / metabolism, pathology Malaria / immunology*, metabolism, parasitology Mice Mice, Inbred BALB C Plasmodium yoelii / immunology* Sporozoites / physiology* Tumor Necrosis Factor-alpha / metabolism Up-Regulation |
| Grant Support | |
ID/Acronym/Agency:
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R01 AI051656-01/AI/NIAID NIH HHS; R01 AI051656-02/AI/NIAID NIH HHS; R01 AI051656-03/AI/NIAID NIH HHS; R01 AI051656-04/AI/NIAID NIH HHS; R01 AI051656-05/AI/NIAID NIH HHS; R01 AI51656/AI/NIAID NIH HHS; S10 RR019288/RR/NCRR NIH HHS; S10 RR019288-01/RR/NCRR NIH HHS; S10 RR019288-010001/RR/NCRR NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Cytokines; 0/Interleukins; 0/Lipopolysaccharides; 0/Tumor Necrosis Factor-alpha; 28822-58-4/1-Methyl-3-isobutylxanthine; 362-74-3/Bucladesine; 82115-62-6/Interferon-gamma |
| Comments/Corrections | |
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