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

The implication of hyporeresponsiveness to LPS in Lewis astrocytes is not clear. LPS is capable ofinducing IL6 protein production by Lewis astrocytes, and we have also found that LPS inhibits the expression ofIFN-y-induced class II antigens on these same cells (Chung, IY, and E.N. Benveniste, unpublished observation) . Thus, Lewis astrocyte hyporesponsiveness to LPS is not global, but seems to be restricted to TNF-a gene expression. In C3H/Hej mice (endotoxin resistant), peritoneal macrophages produce no detectable TNF-a protein, even when expressing TNF-a mRNA (40) . It has been suggested that a dual defect prevents TNF-ci expression in these mice; high concentrations of LPS are required to induce TNF-a mRNA levels within the cell, and a posttranscriptional defect prevents the translation of the mRNA to TNF-a protein . Our findings are somewhat similar, although low levels of TNF-ca mRNA are detected in LPStreated Lewis astrorytes even when high concentrations of LPS (10 leg/ml) are used for stimulation . This would suggest a partial transcriptional block, which can not be overcome by using high concentrations ofLPS, as well as a posttranscriptional defect .