Expression of IP-10, a lipopolysaccharide- and interferon-gamma-inducible protein, in murine mesangial cells in culture.
IP-10 is an early gene induced in multiple cell types by a variety of proinflammatory agents, notably interferons (IFNs) and lipopolysaccharide (LPS). To determine whether this protein might play a role in amplifying immune-mediated glomerular injury, we cultured mouse mesangial cells with several stimuli for various times. Increasing amounts of IFN-gamma (to 100 units/ml) elicited increasing levels of IP-10 messenger RNA (mRNA), sustained to 24 hours, but had no effect on tumor necrosis factor-alpha (TNF-alpha) mRNA. LPS induced transient IP-10 mRNA expression that peaked at 8 hours; TNF-alpha mRNA was also increased. TNF-alpha at doses up to 10 ng/ml and soluble immune complexes up to 150 micrograms/ml antibody evoked 3- to 5-fold increases in IP-10 mRNA expression, much less than the 30- to 70-fold increases seen with IFN-gamma and LPS. We conclude that IFN-gamma, LPS, and other agonists can amplify glomerular immune injury, perhaps via elevated expression of IP-10.
Gómez-Chiarri
M
M
Renal Unit, Fundación Jiménez Díaz, Madrid, Spain.
Hamilton
T A
TA
Egido
J
J
Emancipator
S N
SN
D000818:Animals; D002478:Cells, Cultured; D054357:Chemokine CXCL10; D019743:Chemokines, CXC; D003513:Cycloheximide / Q000494:pharmacology; D016207:Cytokines / Q000235:genetics / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D005920:Glomerular Mesangium / Q000166:cytology / Q000378:metabolism*; D007371:Interferon-gamma / Q000494:pharmacology*; D008070:Lipopolysaccharides / Q000494:pharmacology*; D051379:Mice; D012333:RNA, Messenger / Q000378:metabolism; D013997:Time Factors
D054357:Chemokine CXCL10; D019743:Chemokines, CXC; D016207:Cytokines; D008070:Lipopolysaccharides; D012333:RNA, Messenger; D007371:Interferon-gamma; D003513:Cycloheximide