EXPRESSION OF IP-10, A LIPOPOLYSACCHARIDE-GAMMA-INDUCIBLE 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 bad 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 mug/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.