Allam, Ramanjaneyulu, Lichtnekert, Julia, Moll, Anton G., Taubitz, Anela, Vielhauer, Volker und Anders, Hans-Joachim
(2009)
Viral RNA and DNA trigger common antiviral responses in mesangial cells.
Journal of the American Society of Nephrology : JASN 20 (9), S. 1986-1996.
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Zusammenfassung
Extrarenal viral infections commonly trigger glomerulonephritis, usually in association with immune complex disease. The Ig component of immune complexes can activate glomerular cell Fc receptors, but whether complexed viral nucleic acids contribute to glomerular inflammation remains unknown. Because of the types of Toll-like receptors (Tlrs) expressed by glomerular mesangial cells, we ...
Zusammenfassung
Extrarenal viral infections commonly trigger glomerulonephritis, usually in association with immune complex disease. The Ig component of immune complexes can activate glomerular cell Fc receptors, but whether complexed viral nucleic acids contribute to glomerular inflammation remains unknown. Because of the types of Toll-like receptors (Tlrs) expressed by glomerular mesangial cells, we hypothesized that viral single-stranded RNA and DNA would activate mesangial cells via Tlr-independent pathways and trigger overlapping antiviral immune responses. Consistent with this hypothesis, 5'-triphosphate RNA (3P-RNA) and non-CpG DNA activated murine primary glomerular mesangial cells to secrete Cxcl10 and Il-6 even in cells derived from mice deficient in the Tlr adaptor proteins Myd88 and Trif. Transcriptome analysis revealed that 3P-RNA and non-CpG-DNA triggered almost identical gene expression programs, especially the proinflammatory cytokine Il-6, several chemokines, and genes related to type I IFN. We observed similar findings in glomerular preparations after injecting 3P-RNA and non-CpG-DNA in vivo. These effects depended on the formation of complexes with cationic lipids, which enhanced nucleic acid uptake into the cytosol of mesangial cells. Small interfering RNA studies revealed that 3P-RNA recognition involves Rig-1, whereas non-CpG-DNA did not require Rig-1 or Dai to activate glomerular mesangial cells. We conclude that 3P-RNA and double-stranded DNA trigger a common, TLR-independent, antiviral response in glomerular mesangial cells, which may promote glomerulonephritis in the setting of viral infection.
Bibliographische Daten exportieren
| Dokumentenart: | Artikel |
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| Datum: | September 2009 |
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| Institutionen: | Medizin > Institut für Funktionelle Genomik > Lehrstuhl für Statistische Bioinformatik (Prof. Spang) |
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| Identifikationsnummer: | | Wert | Typ |
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| 19713315 | PubMed-ID | | 10.1681/ASN.2008101067 | DOI |
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| Klassifikation: | | Notation | Art |
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| Animals | MESH | | Apoptosis/immunology | MESH | | Cell Line | MESH | | Chemokine CXCL10/metabolism | MESH | | CpG Islands/immunology | MESH | | DNA, Viral/immunology | MESH | | Female | MESH | | Gene Expression/immunology | MESH | | Glomerulonephritis/virology | MESH | | Glycoproteins/metabolism | MESH | | Immune Complex Diseases/virology | MESH | | Interferons/metabolism | MESH | | Interleukin-6/metabolism | MESH | | Membrane Proteins/metabolism | MESH | | Mesangial Cells/virology | MESH | | Mice | MESH | | Mice, Inbred C57BL | MESH | | Nerve Tissue Proteins/metabolism | MESH | | Oligonucleotide Array Sequence Analysis | MESH | | RNA, Viral/immunology | MESH |
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| Dewey-Dezimal-Klassifikation: | 600 Technik, Medizin, angewandte Wissenschaften > 610 Medizin |
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| Status: | Veröffentlicht |
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| Begutachtet: | Ja, diese Version wurde begutachtet |
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| An der Universität Regensburg entstanden: | Nein |
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| Eingebracht am: | 19 Aug 2014 07:47 |
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| Zuletzt geändert: | 18 Jan 2016 12:46 |
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| Dokumenten-ID: | 30670 |
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