Abstract
In viral infections, disease manifestations and tissue damage often result primarily from immune cells infiltrating target organs on the basis of an ineffectual viral clearance with persistent antigenemia or an inappropriate immune response. Cell types and mediators defining these inflammatory processes are still inadequately understood. In hepatitis C virus-associated glomerulonephritis, analysis of interferon-γ-inducible protein (IP-10) as a chemokine centrally involved in early antiviral response and TNF-α known to balance proinflammatory and immunosuppressive effects in inflammation shows a significant upregulation of both IP-10 and TNF-α mediated specifically by the viral receptor Toll-like receptor 3 expressed on mesangial cells. IP-10 induction is further potentiated by TNF-α signaling, preferentially via the TNF-α receptor subtype 2 selectively increased upon stimulation of viral receptors in the proinflammatory milieu.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Antiviral Agents / pharmacology
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Cell Movement / drug effects
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Cell Proliferation / drug effects
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Cells, Cultured
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Chemokine CXCL10 / physiology*
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Chemokines / biosynthesis
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Cytokines / biosynthesis*
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Glomerular Mesangium / cytology
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Glomerular Mesangium / metabolism*
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Glomerulonephritis / etiology
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Glomerulonephritis / pathology*
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Hepatitis C / complications
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Hepatitis C / pathology*
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Humans
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Interferon Type I / biosynthesis
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Interleukin-1beta / biosynthesis
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Poly I-C / pharmacology
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RNA, Small Interfering
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RNA, Viral / chemistry
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RNA, Viral / genetics
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RNA, Viral / isolation & purification
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Receptors, Retinoic Acid / biosynthesis
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Receptors, Retinoic Acid / genetics
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Receptors, Tumor Necrosis Factor, Type I / biosynthesis
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Receptors, Tumor Necrosis Factor, Type I / genetics
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Receptors, Tumor Necrosis Factor, Type II / biosynthesis
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Receptors, Tumor Necrosis Factor, Type II / genetics
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Reverse Transcriptase Polymerase Chain Reaction
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Toll-Like Receptor 3 / genetics
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Toll-Like Receptor 3 / physiology*
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Transfection
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Tumor Necrosis Factor-alpha / biosynthesis
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Tumor Necrosis Factor-alpha / physiology*
Substances
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Antiviral Agents
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CXCL10 protein, human
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Chemokine CXCL10
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Chemokines
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Cytokines
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Interferon Type I
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Interleukin-1beta
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PLAAT4 protein, human
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RNA, Small Interfering
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RNA, Viral
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Receptors, Retinoic Acid
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Receptors, Tumor Necrosis Factor, Type I
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Receptors, Tumor Necrosis Factor, Type II
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Toll-Like Receptor 3
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Tumor Necrosis Factor-alpha
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Poly I-C