1. Prostaglandin E2 Affects Differently the Release of Inflammatory Mediators from Resident Macrophages by LPS and Muramyl Tripeptides
- Author
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Sabine Kamionka, Thuy-Anh Tran-Thi, Birgit Malessa, Edith Fitzke, Peter Dieter, Ute Hempel, and Angelika Kolada
- Subjects
Cytotoxicity, Immunologic ,Lipopolysaccharides ,Male ,Eicosanoids ,Nitric Oxide Synthase Type II ,Pharmacology ,chemistry.chemical_compound ,Drug Interactions ,Prostaglandin E2 ,Protein Kinase C ,Mitogen-Activated Protein Kinase 1 ,Mitogen-Activated Protein Kinase 3 ,NF-kappa B ,Muramyl tripeptides ,Nitric oxide synthase ,Cytokines ,Tumor necrosis factor alpha ,lipids (amino acids, peptides, and proteins) ,Inflammation Mediators ,Mitogen-Activated Protein Kinases ,Signal transduction ,Acetylmuramyl-Alanyl-Isoglutamine ,Signal Transduction ,Research Article ,medicine.drug ,lcsh:RB1-214 ,medicine.medical_specialty ,LPS ,Kupffer Cells ,Immunology ,Prostaglandin ,Biology ,Nitric Oxide ,Dinoprostone ,Nitric oxide ,Internal medicine ,medicine ,lcsh:Pathology ,Animals ,Rats, Wistar ,Protein kinase C ,Tumor Necrosis Factor-alpha ,Macrophages ,Cell Biology ,Rats ,Transcription Factor AP-1 ,Endocrinology ,chemistry ,Prostaglandins ,biology.protein ,Calcium ,Cyclooxygenase ,Nitric Oxide Synthase - Abstract
LPS and MTP-PE (liposome-encapsulatedN-acetylmuramyl-L-alanyl-D-isoglutaminyl-L-alanine-2-:[1',2'-dipalmitoyl-sni-glycero-3-(hydroxy-phosphoryl-oxyl)] etylamide) induce in liver macrophages a synthesis and release of TNF-α, nitric oxide and prostanoids. Both agents induce an expression of mRNA's encoding TNF-α, inducible nitric oxide synthase (iNOS) and cyclooxygenase (COX)-2, and of corresponding proteins. LPS and MTP-PE induce a rapid activation of the extracellular regulated kinase (ERK) isoenzymes-1 and -2. Inhibition of map kinase isoenzymes leads to a decreased release of TNF-α, nitric oxide and prostaglandin (PG) E2after both agents. The transcription factors NF-κB and AP-1 are strongly activated by LPS within 30 minutes. MTP-PE induces a weak activation of both transcription factors only after 5 hours. Inhibition of NF-κB inhibits the LPS- but not the MTP-PE-induced release of TNF-α, nitric oxide and PGE2. PGE2release after LPS is higher than after MTP-PE. Exogenously added PGE2inhibits the activation of map kinase and TNF-α release by LPS, but not by MTP-PE. Release of nitric oxide after LPS and MTP-PE is enhanced after prior addition of PGE2. PGD2is without any effect. MTP-PE, but not LPS, induces a cytotoxicity of Kupffer cells against P815 tumor target cells. The MTP-PE-induced cytotoxicity is reduced by TNF-α neutralizing antibodies, indicating the involvement of TNF-α. Thus our results suggest that the different potencies of LPS and MTP-PE as immunomodulators probably result from different actions on Kupffer cells, resulting in differences in the amounts and kinetics of released TNF-α and PGE2, and that PGE2plays an important regulatory role in the action of LPS, but not in the actions of MTP-PE.
- Published
- 1999