Interferon-β Reduces Proteinuria in Experimental Glomerulonephritis

Abstract

Interferon-␤ (IFN-␤) is a multifunctional cytokine with immunomodulatory properties. We examined the effect of IFN-␤ in three separate rat models of glomerular injury and in cultured human glomerular endothelial cells and podocytes. In nephrotoxic nephritis in WKY rats, recombinant rat IFN-␤ started either at induction or after establishment of disease significantly reduced 24-h proteinuria by up to 73% and 51%, respectively, but did not affect serum creatinine. There was a slight reduction in numbers of glomerular macrophages, but no difference in glomerular or tubulointerstitial scarring. In Thy-1 nephritis in Lewis rats, IFN-␤ started at induction of disease reduced proteinuria by up to 66% with no effect on numbers of glomerular macrophages, but a reduced number of proliferating cells. In puromycin nephropathy in Wistar rats, IFN-␤ started at induction of disease reduced proteinuria by up to 93%, but had no effect on glomerular histology. In cultured cells, human IFN-␤-1a had a dramatic effect on barrier properties, increasing electrical resistance across monolayers of either glomerular endothelial cells or podocytes and decreasing trans-monolayer passage of albumin. In conclusion, these results show that IFN-␤ reduces proteinuria in three different rat models of glomerular injury and that its anti-proteinuric action may result from direct effects on cells that comprise the glomerular filtration barrier. These data indicate that IFN-␤ may have potential as a therapeutic agent in proteinuric renal disease.

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

“…Very interestingly, we can show that IP-10, while not having any effect on the expression of MCP-1 and IL-6, strongly induces IFN-␤. As type I interferons are known to be relevant not only for early antiviral responses (12) but IFN-␤ has been shown to exert antiproteinuric effects (20), a protective effect of IP-10 in early viral infection by induction of IFN-␤ can be postulated.…”

Insulin Signaling to the Glomerular Podocyte Is Critical for Normal Kidney Function

“…Time course analysis and resistance measurement was performed using an automated cell monitoring system ‘Electrical Cell-Substrate Impedance Sensing’ (ECIS 1600R, Applied Biophysics, Rochester, NY) as recently described (Satchell et al, 2007). This detects nanometre scale changes in cell morphology, in real time, by virtue of the changes in electrical resistance it detects.…”

Double-Stranded DNA Activates Glomerular Endothelial Cells and Enhances Albumin Permeability via a Toll-Like Receptor-Independent Cytosolic DNA Recognition Pathway

“…17,21 FITC-labeled bovine serum albumin (Invitrogen) was added to inserts and the cells were stimulated with 10 g/ml B-DNA/CL or 6 g/ml CpG-DNA. The filtrate was sampled at different time points and OD was measured at 485 nm and emission at 535 nm.…”