TUMOR-NECROSIS-FACTOR INDUCES LIPOPOLYSACCHARIDE TOLERANCE IN A HUMANADENOCARCINOMA CELL-LINE MAINLY THROUGH THE TNF P55 RECEPTOR

This study demonstrates that lipopolysaccharide (LPS) mediates inducti on of transcription factor NF kappa B and activation of the cytomegalo virus (CMV) promoter-enhancer in the SW480 cell Line. These cells do n ot express a functional membrane CD14. The LPS response in SW480 cells was weaker and markedly slower than the tumor necrosis factor (TNF) r esponse. Pretreatment with TNF for 72 h inhibited both TNF, tumor necr osis factor receptor (TNFR) p55, TNFR p75, and LPS-mediated activation of nuclear factor -kappa B (NF kappa B), whereas pretreatment with LP S only inhibited the LPS response. TNFR p55 antibody pretreatment resu lted in marked inhibition of the LPS response, while pretreatment with TNFR p75 antiserum only had a weak inhibitory effect. Flowcytometric analysis showed that LPS binding as well as expression of TNFR p55 and TNFR p75 were not affected by LPS or TNF pretreatment, indicating tha t the observed inhibition is not due to reduction of specific binding sites at the cell surface. The results suggest that LPS signaling in S W480 cells involves intracellular components which may be depleted or inactivated via TNFR p55, indicating that the LPS and TNFR p55 pathway s overlap. We propose that TNFR p55 can mediate activation of NF kappa B and cytomegalovirus promoter-enhancer in SW480 cells via two distin ct mechanisms, one which is activated only via TNFR p55 and leads to r apid activation of NF kappa B, and another which is overlapping with t he LPS pathway.