TY - JOUR
T1 - Interferon-gamma augments acute macrophage-mediated renal injury via a glucocorticoid-sensitive mechanism
AU - Ikezumi, Yohei
AU - Atkins, Robert Charles
AU - Nikolic-Paterson, David J
PY - 2003
Y1 - 2003
N2 - SUMMARY:
Macrophage migration inhibitory factor (MIF) promotes macrophage accumulation and leucocyte activation during inflammation. Macrophage migration inhibitory factor is upregulated in intrinsic renal cells in many types of kidney diseases, and has a pathogenic role in rat crescentic
nephritis. However, little is known about the factors that regulate the production and secretion of MIF in kidney cells. In this study, we evaluated whether interferon-gamma (IFNg ), a cytokine implicated in
the development of kidney disease and a potent inducer of MIF production in macrophages, could promote MIF synthesis and secretion from renal tubular epithelial cells. Northern blot analysis detected constitutive expression of MIF mRNA in rat tubular epithelial cells (NRK52E), which increased twofold
after a 6-h stimulation with IFNg . Macrophage migration inhibitory factor protein was found only in the cytoplasm of NRK52E cells. Following IFNg
stimulation, intracellular MIF in NRK52E cells was rapidly secreted with a maximal reduction of 50 after 20 min, which returned to normal levels after 2a??4 h. Rapid secretion of MIF in response to IFNg was also seen in rat mesangial cells. These findings indicate that IFNg induces rapid secretion of MIF by tubular epithelial cells, and suggest that this may be an important mechanism leading to inflammatory cell accumulation and activation during kidney disease.
AB - SUMMARY:
Macrophage migration inhibitory factor (MIF) promotes macrophage accumulation and leucocyte activation during inflammation. Macrophage migration inhibitory factor is upregulated in intrinsic renal cells in many types of kidney diseases, and has a pathogenic role in rat crescentic
nephritis. However, little is known about the factors that regulate the production and secretion of MIF in kidney cells. In this study, we evaluated whether interferon-gamma (IFNg ), a cytokine implicated in
the development of kidney disease and a potent inducer of MIF production in macrophages, could promote MIF synthesis and secretion from renal tubular epithelial cells. Northern blot analysis detected constitutive expression of MIF mRNA in rat tubular epithelial cells (NRK52E), which increased twofold
after a 6-h stimulation with IFNg . Macrophage migration inhibitory factor protein was found only in the cytoplasm of NRK52E cells. Following IFNg
stimulation, intracellular MIF in NRK52E cells was rapidly secreted with a maximal reduction of 50 after 20 min, which returned to normal levels after 2a??4 h. Rapid secretion of MIF in response to IFNg was also seen in rat mesangial cells. These findings indicate that IFNg induces rapid secretion of MIF by tubular epithelial cells, and suggest that this may be an important mechanism leading to inflammatory cell accumulation and activation during kidney disease.
UR - http://jasn.asnjournals.org/cgi/reprint/14/4/888
U2 - 10.1097/01.ASN.0000056604.13964.62
DO - 10.1097/01.ASN.0000056604.13964.62
M3 - Article
VL - 14
SP - 888
EP - 898
JO - Journal of the American Society of Nephrology
JF - Journal of the American Society of Nephrology
SN - 1046-6673
IS - 4
ER -