Interferon-inducible protein-10 is highly expressed in rats with experimental nephrosis.
Interferon-inducible protein (IP)-10 is a small glycoprotein member of a family of chemotactic cytokines structurally related to interleukin-8. We have recently described the induction of IP-10 mRNA in mouse mesangial cells stimulated with lipopolysacharide, interferon-gamma, and tumor necrosis factor-alpha. To further evaluate a possible role for this chemokine in renal injury, we have studied IP-10 in an experimental model of nephrosis induced in rats by adriamycin. High levels of glomerular IP-10 mRNA expression and glomerular and tubulointerstitial IP-10 protein were seen on day 21, coinciding with maximal proteinuria, glomerular tumor necrosis factor mRNA expression, and interstitial cellular infiltrates. Maintenance on a low protein diet not only delayed the appearance of proteinuria and interstitial cellular infiltrate but also decreased glomerular IP-10 mRNA expression. Isolated normal glomeruli and cultured glomerular epithelial and mesangial cells from normal rats expressed IP-10 mRNA upon stimulation with 100 U/ml interferon or 1 microgram/ml lipopolysaccharide for 3 hours. IP-10 mRNA expression was also inducible by lipopolysaccharide and cytokines in NRK 49F renal interstitial fibroblasts and, to a lesser extent, in NRK 52E tubular epithelial cells. Furthermore, IP-10 protein was inducible in murine mesangial cells. We conclude that IP-10 is highly inducible in vitro and in vivo in resident glomerular and tubulointerstitial cells. IP-10 may participate in the modulation of renal damage in experimental nephrosis.
Fundación Jiménez Díaz, Madrid, Spain.
M
M
Gómez-Chiarri
A
A
Ortiz
S
S
González-Cuadrado
D
D
Serón
S N
SN
Emancipator
T A
TA
Hamilton
A
A
Barat
J J
JJ
Plaza
E
E
González
J
J
Egido
D000818:Animals; D001483:Base Sequence; D002478:Cells, Cultured; D054357:Chemokine CXCL10; D019743:Chemokines, CXC; D016207:Cytokines / Q000378:metabolism*; D004317:Doxorubicin; D005260:Female; D016130:Immunophenotyping; D007678:Kidney Glomerulus / Q000378:metabolism*; D007684:Kidney Tubules / Q000378:metabolism*; D008213:Lymphocyte Activation; D051379:Mice; D008969:Molecular Sequence Data; D009401:Nephrosis / Q000139:chemically induced / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors
D054357:Chemokine CXCL10; D019743:Chemokines, CXC; D016207:Cytokines; D012333:RNA, Messenger; D004317:Doxorubicin