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 inflam matory and immune responses. Its biological action is crucially depend ent on interaction with specific cell surface receptors. Two different receptors for TNF-alpha with molecular masses of 55 and 75 kDa have b een described. Here, the presence of a 55 kDa TNF receptor mRNA and th e expression of its protein is demonstrated in rat liver Kupffer cells . TNF-alpha receptor was purified from detergent-solubilized rat Kupff er cells by adsorption to recombinant human TNF-alpha-Sepharose. One b and 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 t he exposure of Kupffer cells to LPS decreased the binding of (125)l-la belled TNF-alpha. Interferon-gamma clearly enhanced the level of 55 kD a TNF-R mRNA; this effect was abolished by transcriptional but not by translational inhibitors. The increase in 55 kDa TNF-R mRNA was maxima l at 2-4h of exposure of IFN-gamma. This cytokine also increased the b inding of (125)l-TNF-alpha to Kupffer cells. On the other hand, the am ount of 55 kDa TNF-R transcripts was reduced after treatment with dexa methasone. These data suggest that in Kupffer cells the expression of the 55 kDa TNF-R is regulated at the transcriptional level.