RAT-LIVER MACROPHAGES EXPRESS THE 55 KDA TUMOR-NECROSIS-FACTOR RECEPTOR - MODULATION BY INTERFERON-GAMMA, LIPOPOLYSACCHARIDE AND TUMOR-NECROSIS-FACTOR-ALPHA

Tumor necrosis factor-alpha is an important mediator of various inflammatory and immune responses. Its biological action is crucially dependent on interaction with specific cell surface receptors. Two different receptors for TNF-alpha with molecular masses of 55 and 75 kDa have been described. Here, the presence of a 55 kDa TNF receptor mRNA and the expression of its protein is demonstrated in rat liver Kupffer cells. TNF-alpha receptor was purified from detergent-solubilized rat Kupffer cells by adsorption to recombinant human TNF-alpha-Sepharose. One band of approx. 55kDa was seen in SDS PAGE. An antibody raised against the 55 kDa TNF receptor bound specifically to the purified receptor as revealed by immunoblot analysis. Using Northern blotting, neither LPS nor TNF-alpha altered the expression of 55 kDa TNF-R mRNA, although the exposure of Kupffer cells to LPS decreased the binding of (125)l-labelled TNF-alpha. Interferon-gamma clearly enhanced the level of 55 kDa TNF-R mRNA; this effect was abolished by transcriptional but not by translational inhibitors. The increase in 55 kDa TNF-R mRNA was maximal at 2-4h of exposure of IFN-gamma. This cytokine also increased the binding of (125)l-TNF-alpha to Kupffer cells. On the other hand, the amount of 55 kDa TNF-R transcripts was reduced after treatment with dexamethasone. These data suggest that in Kupffer cells the expression of the 55 kDa TNF-R is regulated at the transcriptional level.