Differential tumor necrosis factor alpha expression by astrocytes from experimental allergic encephalomyelitis-susceptible and -resistant rat strains

We have previously demonstrated that astrorytes from the outbred rat strain Sprague Dawley secrete TNF-a in response to LPS alone, IFN-y plus LPS, and IFN-y plus ID10 (11). IFN-y alone does not induce TNF-cx production by astrocytes but acts to enhance LPS-induced TNF-a synthesis and to synergize with Ilrlf for TNF-a production. The most potent TNF-a production is observed when astrorytes are pretreated with IFN-y for 8-12 h before exposure to either LPS or IIr1/3, suggesting that IFN-y provides a priming signal to the astrocyte . The aim of this study was to examine TNF-a expression by astrocytes from inbred BN and Lewis rats in response to the three different stimuli . We report that TNF-a expression at both the mRNA and protein level is differentially regulated in these strains depending upon the stimuli used for induction . Astrocytes from EAE-resistant BN rats are refractive to the priming effect of IFN-y for enhanced LPS-induced TNF-a production, and produce very low levels of TNF-a in response to IFN-y/IIr1O . In contrast, astrocytes from EAE-susceptible Lewis rats are hyporesponsive to the LPS induction signal, and extremely sensitive to the priming effect of IFN-y for subsequent TNF-a production . Also, Lewis astrocytes produce high levels of TNF-a when stimulated by IFN-y and IIAO. Thus, Lewis and BN astrocytes are differentially regulated by LPS and IFN-y with respect to TNF-a gene expression.