APPLICATION OF INHIBITOR ANALYSIS FOR STUDYING MECHANISMS AND ACTIONS OF POLYMURAMYL, A MURAMYL PEPTIDE-BASED IMMUNE MODULATOR

In present study, the following low-MW inhibitors were used to dissect mechanisms of action for two muramyl peptide components of Polymuramyl, an immunomodulatory drug: (1) N-acetyl-D-glucosaminyl-(β1→4)-N-acetyl-D-muramoyl-L-alanyl-D-isoglutaminyl-meso-diaminopimelic acid (GMtri); (2) a dimeric m...

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Autores principales:	M. V. Pashenkov, B. I. Alkhazova, V. L. L'vov, B. V. Pinegin
Formato:	article
Lenguaje:	RU
Publicado:	SPb RAACI 2014
Materias:	muramyl peptides macrophages sb203580 genistein tumor necrosis factor Immunologic diseases. Allergy RC581-607
Acceso en línea:	https://doaj.org/article/db6b35ba9c5048e3a0daf4c792ec858c
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spelling	oai:doaj.org-article:db6b35ba9c5048e3a0daf4c792ec858c2021-11-18T08:03:37ZAPPLICATION OF INHIBITOR ANALYSIS FOR STUDYING MECHANISMS AND ACTIONS OF POLYMURAMYL, A MURAMYL PEPTIDE-BASED IMMUNE MODULATOR1563-06252313-741X10.15789/1563-0625-2013-1-21-28https://doaj.org/article/db6b35ba9c5048e3a0daf4c792ec858c2014-07-01T00:00:00Zhttps://www.mimmun.ru/mimmun/article/view/59https://doaj.org/toc/1563-0625https://doaj.org/toc/2313-741XIn present study, the following low-MW inhibitors were used to dissect mechanisms of action for two muramyl peptide components of Polymuramyl, an immunomodulatory drug: (1) N-acetyl-D-glucosaminyl-(β1→4)-N-acetyl-D-muramoyl-L-alanyl-D-isoglutaminyl-meso-diaminopimelic acid (GMtri); (2) a dimeric muramyl peptide (diGMtetra), wherein two monomers [N-acetyl-D-glucosaminyl-(β1→4)-N-acetyl-D-muramoyl-L-alanyl-D-isoglutaminyl-meso-diaminopimeloyl-D-alanin] are linked via an amide bond between the carboxyl group of terminal D-alanin at one monomer and the ω-amino group of meso-diaminopimelic acid at another monomer. In vitro production of tumor necrosis factor (TNF) by human macrophages stimulated with GMtri or diGMtetra was shown to be inhibited by SB203580 (a RIP2 kinase inhibitor), genistein (a protein tyrosine kinase inhibitor) and BAY 11-7082 (an IκB-kinase inhibitor). Moreover, response to diGMtetra was inhibited by dynasore (an inhibitor of clathrin-dependent endocytosis), as well as by a broad-range protease-inhibiting cocktail. Thus, activating effects upon macrophages induced by the Polymuramyl components is provided by, at least, three biological processes: (1) clathrin-dependent endocytosis; (2) peptidase-mediated processing of diGMtetra; 3) activation of a signal chain RIP2 – IκB-kinase – NF-κB transcription factor.M. V. PashenkovB. I. AlkhazovaV. L. L'vovB. V. PineginSPb RAACIarticlemuramyl peptidesmacrophagessb203580genisteintumor necrosis factorImmunologic diseases. AllergyRC581-607RUMedicinskaâ Immunologiâ, Vol 15, Iss 1, Pp 21-28 (2014)
institution	DOAJ
collection	DOAJ
language	RU
topic	muramyl peptides macrophages sb203580 genistein tumor necrosis factor Immunologic diseases. Allergy RC581-607
spellingShingle	muramyl peptides macrophages sb203580 genistein tumor necrosis factor Immunologic diseases. Allergy RC581-607 M. V. Pashenkov B. I. Alkhazova V. L. L'vov B. V. Pinegin APPLICATION OF INHIBITOR ANALYSIS FOR STUDYING MECHANISMS AND ACTIONS OF POLYMURAMYL, A MURAMYL PEPTIDE-BASED IMMUNE MODULATOR
description	In present study, the following low-MW inhibitors were used to dissect mechanisms of action for two muramyl peptide components of Polymuramyl, an immunomodulatory drug: (1) N-acetyl-D-glucosaminyl-(β1→4)-N-acetyl-D-muramoyl-L-alanyl-D-isoglutaminyl-meso-diaminopimelic acid (GMtri); (2) a dimeric muramyl peptide (diGMtetra), wherein two monomers [N-acetyl-D-glucosaminyl-(β1→4)-N-acetyl-D-muramoyl-L-alanyl-D-isoglutaminyl-meso-diaminopimeloyl-D-alanin] are linked via an amide bond between the carboxyl group of terminal D-alanin at one monomer and the ω-amino group of meso-diaminopimelic acid at another monomer. In vitro production of tumor necrosis factor (TNF) by human macrophages stimulated with GMtri or diGMtetra was shown to be inhibited by SB203580 (a RIP2 kinase inhibitor), genistein (a protein tyrosine kinase inhibitor) and BAY 11-7082 (an IκB-kinase inhibitor). Moreover, response to diGMtetra was inhibited by dynasore (an inhibitor of clathrin-dependent endocytosis), as well as by a broad-range protease-inhibiting cocktail. Thus, activating effects upon macrophages induced by the Polymuramyl components is provided by, at least, three biological processes: (1) clathrin-dependent endocytosis; (2) peptidase-mediated processing of diGMtetra; 3) activation of a signal chain RIP2 – IκB-kinase – NF-κB transcription factor.
format	article
author	M. V. Pashenkov B. I. Alkhazova V. L. L'vov B. V. Pinegin
author_facet	M. V. Pashenkov B. I. Alkhazova V. L. L'vov B. V. Pinegin
author_sort	M. V. Pashenkov
title	APPLICATION OF INHIBITOR ANALYSIS FOR STUDYING MECHANISMS AND ACTIONS OF POLYMURAMYL, A MURAMYL PEPTIDE-BASED IMMUNE MODULATOR
title_short	APPLICATION OF INHIBITOR ANALYSIS FOR STUDYING MECHANISMS AND ACTIONS OF POLYMURAMYL, A MURAMYL PEPTIDE-BASED IMMUNE MODULATOR
title_full	APPLICATION OF INHIBITOR ANALYSIS FOR STUDYING MECHANISMS AND ACTIONS OF POLYMURAMYL, A MURAMYL PEPTIDE-BASED IMMUNE MODULATOR
title_fullStr	APPLICATION OF INHIBITOR ANALYSIS FOR STUDYING MECHANISMS AND ACTIONS OF POLYMURAMYL, A MURAMYL PEPTIDE-BASED IMMUNE MODULATOR
title_full_unstemmed	APPLICATION OF INHIBITOR ANALYSIS FOR STUDYING MECHANISMS AND ACTIONS OF POLYMURAMYL, A MURAMYL PEPTIDE-BASED IMMUNE MODULATOR
title_sort	application of inhibitor analysis for studying mechanisms and actions of polymuramyl, a muramyl peptide-based immune modulator
publisher	SPb RAACI
publishDate	2014
url	https://doaj.org/article/db6b35ba9c5048e3a0daf4c792ec858c
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APPLICATION OF INHIBITOR ANALYSIS FOR STUDYING MECHANISMS AND ACTIONS OF POLYMURAMYL, A MURAMYL PEPTIDE-BASED IMMUNE MODULATOR

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