TLR3-dependent regulation of cytokines in human mesangial cells: a novel role for IP-10 and TNF-α in hepatitis C-associated glomerulonephritis

Merkle M, Ribeiro A, Wornle M. TLR3-dependent regulation of cytokines in human mesangial cells: a novel role for IP-10 and TNF-alpha in hepatitis C-associated glomerulonephritis. Am J Physiol Renal Physiol 301: F57-F69, 2011. First published March 30, 2011; doi: 10.1152/ajprenal.00083.2011.-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-gamma-inducible protein (IP-10) as a chemokine centrally involved in early antiviral response and TNF-alpha known to balance proinflammatory and immunosuppressive effects in inflammation shows a significant upregulation of both IP-10 and TNF-alpha mediated specifically by the viral receptor Toll-like receptor 3 expressed on mesangial cells. IP-10 induction is further potentiated by TNF-alpha signaling, preferentially via the TNF-alpha receptor subtype 2 selectively increased upon stimulation of viral receptors in the proinflammatory milieu.