Production of factors involved into fibrosis regulation by various types of human macrophages

Macrophages (Mφ) play a key role in regulation of fibrogenesis, including proliferation of fibroblasts and myofibroblasts, differentiation of progenitor cells into myofibroblasts, as well as synthesis and secretion of the extracellular matrix, mainly collagen. The direction of the Mφ effect...

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Autores principales:	A. A. Maksimova, E. Ya. Shevela, L. V. Sakhno, A. A. Ostanin, E. R. Chernykh
Formato:	article
Lenguaje:	RU
Publicado:	SPb RAACI 2020
Materias:	macrophages polarization cytokines matrix metalloproteinases inhibitors of matrix metalloproteinases fibrosis Immunologic diseases. Allergy RC581-607
Acceso en línea:	https://doaj.org/article/19996ec7cc064568a449a7e431a189af
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spelling	oai:doaj.org-article:19996ec7cc064568a449a7e431a189af2021-11-18T08:03:49ZProduction of factors involved into fibrosis regulation by various types of human macrophages1563-06252313-741X10.15789/1563-0625-POF-1954https://doaj.org/article/19996ec7cc064568a449a7e431a189af2020-08-01T00:00:00Zhttps://www.mimmun.ru/mimmun/article/view/1954https://doaj.org/toc/1563-0625https://doaj.org/toc/2313-741XMacrophages (Mφ) play a key role in regulation of fibrogenesis, including proliferation of fibroblasts and myofibroblasts, differentiation of progenitor cells into myofibroblasts, as well as synthesis and secretion of the extracellular matrix, mainly collagen. The direction of the Mφ effects (stimulation or suppression) is determined by a number of factors, including the stage of the fibrotic process and the Mφ functional phenotype dependent on the signals of microenvironment. One of the feasible ways of the fibrogenesis regulating is the secretion of pro- or antifibrotic factors such as matrix metalloproteinases, inhibitors of metalloproteinases and some cytokines. However, existing data on ability to secrete these factors by various subpopulations of human Mφ are rare and controversial. The aim of this study was to characterize the ability of human M1, M2a, and M2c Mφ differentiating in the presence of GM-CSF to produce matrix metalloproteinases (MMP-9) and their tissue inhibitors (TIMP-1), as well as some cytokines and growth factors. As compared to M2 macrophages, the M1 macrophages polarized by lipopolysaccharide produced significantly more TNFα, IL-6 and IL-2 that have pro-inflammatory activity and are able to initiate a fibrotic process. In turn, M2a Mφ stimulated by IL-4 were characterized by a high level of VEGF production and, at the same time, low levels of TNFα and IL-6, which may determine the important role of these cells at the proliferative stage of fibrosis and stimulation of extracellular matrix deposition. Finally, M2c Mφ polarized by dexamethasone, exhibited the М2а-like cytokine profile, i.e., VEGF was actively produced against the background of low TNFα and IL-6 synthesis. Moreover, all three Mφ subpopulations did actively secrete MMP-9 and TIMP-1, without significant difference in production of these factors. However, M2c Mφ differed by a significantly higher MMP-9/TIMP-1 ratio index compared to M1 and M2a Mφ, and it is crucial at the rearrangement stage of the fibrotic process. Thus, the production of MMP-9 and TIMP-1, together with other pleiotropic cytokines and growth factors by various Mφ subtypes may reflect their role in regulation of fibrotic process at various stages.A. A. MaksimovaE. Ya. ShevelaL. V. SakhnoA. A. OstaninE. R. ChernykhSPb RAACIarticlemacrophagespolarizationcytokinesmatrix metalloproteinasesinhibitors of matrix metalloproteinasesfibrosisImmunologic diseases. AllergyRC581-607RUMedicinskaâ Immunologiâ, Vol 22, Iss 4, Pp 625-632 (2020)
institution	DOAJ
collection	DOAJ
language	RU
topic	macrophages polarization cytokines matrix metalloproteinases inhibitors of matrix metalloproteinases fibrosis Immunologic diseases. Allergy RC581-607
spellingShingle	macrophages polarization cytokines matrix metalloproteinases inhibitors of matrix metalloproteinases fibrosis Immunologic diseases. Allergy RC581-607 A. A. Maksimova E. Ya. Shevela L. V. Sakhno A. A. Ostanin E. R. Chernykh Production of factors involved into fibrosis regulation by various types of human macrophages
description	Macrophages (Mφ) play a key role in regulation of fibrogenesis, including proliferation of fibroblasts and myofibroblasts, differentiation of progenitor cells into myofibroblasts, as well as synthesis and secretion of the extracellular matrix, mainly collagen. The direction of the Mφ effects (stimulation or suppression) is determined by a number of factors, including the stage of the fibrotic process and the Mφ functional phenotype dependent on the signals of microenvironment. One of the feasible ways of the fibrogenesis regulating is the secretion of pro- or antifibrotic factors such as matrix metalloproteinases, inhibitors of metalloproteinases and some cytokines. However, existing data on ability to secrete these factors by various subpopulations of human Mφ are rare and controversial. The aim of this study was to characterize the ability of human M1, M2a, and M2c Mφ differentiating in the presence of GM-CSF to produce matrix metalloproteinases (MMP-9) and their tissue inhibitors (TIMP-1), as well as some cytokines and growth factors. As compared to M2 macrophages, the M1 macrophages polarized by lipopolysaccharide produced significantly more TNFα, IL-6 and IL-2 that have pro-inflammatory activity and are able to initiate a fibrotic process. In turn, M2a Mφ stimulated by IL-4 were characterized by a high level of VEGF production and, at the same time, low levels of TNFα and IL-6, which may determine the important role of these cells at the proliferative stage of fibrosis and stimulation of extracellular matrix deposition. Finally, M2c Mφ polarized by dexamethasone, exhibited the М2а-like cytokine profile, i.e., VEGF was actively produced against the background of low TNFα and IL-6 synthesis. Moreover, all three Mφ subpopulations did actively secrete MMP-9 and TIMP-1, without significant difference in production of these factors. However, M2c Mφ differed by a significantly higher MMP-9/TIMP-1 ratio index compared to M1 and M2a Mφ, and it is crucial at the rearrangement stage of the fibrotic process. Thus, the production of MMP-9 and TIMP-1, together with other pleiotropic cytokines and growth factors by various Mφ subtypes may reflect their role in regulation of fibrotic process at various stages.
format	article
author	A. A. Maksimova E. Ya. Shevela L. V. Sakhno A. A. Ostanin E. R. Chernykh
author_facet	A. A. Maksimova E. Ya. Shevela L. V. Sakhno A. A. Ostanin E. R. Chernykh
author_sort	A. A. Maksimova
title	Production of factors involved into fibrosis regulation by various types of human macrophages
title_short	Production of factors involved into fibrosis regulation by various types of human macrophages
title_full	Production of factors involved into fibrosis regulation by various types of human macrophages
title_fullStr	Production of factors involved into fibrosis regulation by various types of human macrophages
title_full_unstemmed	Production of factors involved into fibrosis regulation by various types of human macrophages
title_sort	production of factors involved into fibrosis regulation by various types of human macrophages
publisher	SPb RAACI
publishDate	2020
url	https://doaj.org/article/19996ec7cc064568a449a7e431a189af
work_keys_str_mv	AT aamaksimova productionoffactorsinvolvedintofibrosisregulationbyvarioustypesofhumanmacrophages AT eyashevela productionoffactorsinvolvedintofibrosisregulationbyvarioustypesofhumanmacrophages AT lvsakhno productionoffactorsinvolvedintofibrosisregulationbyvarioustypesofhumanmacrophages AT aaostanin productionoffactorsinvolvedintofibrosisregulationbyvarioustypesofhumanmacrophages AT erchernykh productionoffactorsinvolvedintofibrosisregulationbyvarioustypesofhumanmacrophages
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Production of factors involved into fibrosis regulation by various types of human macrophages

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