Lipopolysaccharide and liposome-encapsulated muramyl tripeptide: Do different responses in Kupffer cells reflect different potencies of the two agents as immunomodulators?

LPS and liposome-encapsulated muramyl tripeptide (MTP-PE) induce in Kupffer cells an activation of the map kinase isoenzymes ERK-1 and ERK-2. The tran scription factors NF-kappa B and AP-1 are activated by lipopolysaccharide ( LPS) within 30 min; MTP-PE induces a weaker activation of NF-kappa B and AP -1, only after 5h. Both immunomodulators induce a release of tumor necrosis Factor (TNF)-alpha, nitric oxide, prostaglandin (PG)E2 and PGD(2) (1). LPS and MTP-PE induce mRNA encoding TNF-alpha, inducible nitric oxide synthase (iNOS) and cyclooxygenase (COX-)2 and corresponding proteins (2). Both imm unomodulators have no effect on mRNA encoding constitutive (c)NOS, COX-1 an d PGD(2) synthase or corresponding proteins (2). Sectretory phospholipase ( sPL)A(2) activity is nor detectable in resting or stimulated Kupffer cells. The observed differences in the activation of the transcription factors NF -kappa B and AP-1 as wll as differences in the formation of TNF-alpha and P GE(2) (1) might reflect the different potencies of LPS and MTP-PE as immuno modulators.