Prostaglandin E2 Affects Differently the Release of Inflammatory Mediators from Resident Macrophages by LPS and Muramyl Tripeptides

LPS and MTP-PE (liposome-encapsulated N-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...

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Main Authors: Peter Dieter, Ute Hempel, Sabine Kamionka, Angelika Kolada, Birgit Malessa, Edith Fitzke, Thuy-Anh Tran-Thi
Format: Article
Language:English
Published: Wiley 1999-01-01
Series:Mediators of Inflammation
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Online Access:http://dx.doi.org/10.1080/09629359990306
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author Peter Dieter
Ute Hempel
Sabine Kamionka
Angelika Kolada
Birgit Malessa
Edith Fitzke
Thuy-Anh Tran-Thi
author_facet Peter Dieter
Ute Hempel
Sabine Kamionka
Angelika Kolada
Birgit Malessa
Edith Fitzke
Thuy-Anh Tran-Thi
author_sort Peter Dieter
collection DOAJ
description LPS and MTP-PE (liposome-encapsulated N-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) E2 after 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. PGE2 release after LPS is higher than after MTP-PE. Exogenously added PGE2 inhibits 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. PGD2 is 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 PGE2 plays an important regulatory role in the action of LPS, but not in the actions of MTP-PE.
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spelling doaj-art-bc5a5b0c699344f88f8aa50f2b5d8e142025-08-20T02:18:43ZengWileyMediators of Inflammation0962-93511466-18611999-01-018629530310.1080/09629359990306Prostaglandin E2 Affects Differently the Release of Inflammatory Mediators from Resident Macrophages by LPS and Muramyl TripeptidesPeter Dieter0Ute Hempel1Sabine Kamionka2Angelika Kolada3Birgit Malessa4Edith Fitzke5Thuy-Anh Tran-Thi6Institute of Physiological Chemistry, Medical Faculty, Dresden University of Technology, Karl-Marx-Strasse 3, Dresden D-01109, GermanyInstitute of Physiological Chemistry, Medical Faculty, Dresden University of Technology, Karl-Marx-Strasse 3, Dresden D-01109, GermanyInstitute of Physiological Chemistry, Medical Faculty, Dresden University of Technology, Karl-Marx-Strasse 3, Dresden D-01109, GermanyInstitute of Physiological Chemistry, Medical Faculty, Dresden University of Technology, Karl-Marx-Strasse 3, Dresden D-01109, GermanyInstitute of Physiological Chemistry, Medical Faculty, Dresden University of Technology, Karl-Marx-Strasse 3, Dresden D-01109, GermanyInstitute of Biochemistry and Molecular Biology, Albert-Ludwigs-University, Freiburg, GermanyInstitute of Biochemistry and Molecular Biology, Albert-Ludwigs-University, Freiburg, GermanyLPS and MTP-PE (liposome-encapsulated N-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) E2 after 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. PGE2 release after LPS is higher than after MTP-PE. Exogenously added PGE2 inhibits 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. PGD2 is 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 PGE2 plays an important regulatory role in the action of LPS, but not in the actions of MTP-PE.http://dx.doi.org/10.1080/09629359990306LPSMacrophagesMuramyl tripeptidesCytokines Eicosanoids.
spellingShingle Peter Dieter
Ute Hempel
Sabine Kamionka
Angelika Kolada
Birgit Malessa
Edith Fitzke
Thuy-Anh Tran-Thi
Prostaglandin E2 Affects Differently the Release of Inflammatory Mediators from Resident Macrophages by LPS and Muramyl Tripeptides
Mediators of Inflammation
LPS
Macrophages
Muramyl tripeptides
Cytokines
Eicosanoids.
title Prostaglandin E2 Affects Differently the Release of Inflammatory Mediators from Resident Macrophages by LPS and Muramyl Tripeptides
title_full Prostaglandin E2 Affects Differently the Release of Inflammatory Mediators from Resident Macrophages by LPS and Muramyl Tripeptides
title_fullStr Prostaglandin E2 Affects Differently the Release of Inflammatory Mediators from Resident Macrophages by LPS and Muramyl Tripeptides
title_full_unstemmed Prostaglandin E2 Affects Differently the Release of Inflammatory Mediators from Resident Macrophages by LPS and Muramyl Tripeptides
title_short Prostaglandin E2 Affects Differently the Release of Inflammatory Mediators from Resident Macrophages by LPS and Muramyl Tripeptides
title_sort prostaglandin e2 affects differently the release of inflammatory mediators from resident macrophages by lps and muramyl tripeptides
topic LPS
Macrophages
Muramyl tripeptides
Cytokines
Eicosanoids.
url http://dx.doi.org/10.1080/09629359990306
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