BCG-INDUCED PRO-INFLAMMATORY PHENOTYPE OF MESENCHYMAL STEM CELLS: EFFECT OF IMMUNE MODULATORS

In case of mycobacterial infection the granulomatous infiltration foci contain the significant amount of mesenchymal stem cells (MSC), which functional phenotype and respective function in anti-tuberculosis immune defense remain unknown.Goal of the study: to characterize the MSC phenotype, formed by...

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Main Authors: A. Sh. Shvarts, S. N. Belogorodtsev, A. E. Petrenko, L. O. Degtyareva, A. I. Shakhmuradova
Format: Article
Language:Russian
Published: New Terra Publishing House 2016-11-01
Series:Туберкулез и болезни лёгких
Subjects:
Online Access:https://www.tibl-journal.com/jour/article/view/957
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author A. Sh. Shvarts
S. N. Belogorodtsev
A. E. Petrenko
L. O. Degtyareva
A. I. Shakhmuradova
author_facet A. Sh. Shvarts
S. N. Belogorodtsev
A. E. Petrenko
L. O. Degtyareva
A. I. Shakhmuradova
author_sort A. Sh. Shvarts
collection DOAJ
description In case of mycobacterial infection the granulomatous infiltration foci contain the significant amount of mesenchymal stem cells (MSC), which functional phenotype and respective function in anti-tuberculosis immune defense remain unknown.Goal of the study: to characterize the MSC phenotype, formed by their interaction with BCG of M. bovis and to evaluate the changes in this phenotype caused by the action of inhibitors and stimulants of immune regulatory action.Materials and methods: MSC retrieved from bone marrow of mice were cultured with the presence and absence of BCG of M. bovis and/or poludanum TLR3 agonist; and the effect of two latter on the production of pro- and anti-inflammatory cytokines was evaluated by enzyme multiplied immunoassay. Flow cytometry and radioactive testing were used to evaluate the impact of cultured BCG fluid and poludanum-conditioned MSC on the proliferative and apoptotic activity of splenocytes. The inhibitors of indoleamine 2,3-dioxygenase (IDO), cyclooxygenase-2 (COG-2) or NO synthase were added to certain cultures alone with BCG and poludanum, and the contributions of IDO, COG-2 and NO to BCG and poludanum-induced response were assessed.Results. Pro-inflammatory polarization of MSC under the action of BCG and poludanum was demonstrated. Pro-inflammatory MSC phenotype correlated to their anti-apoptogenic and growth-stimulating actions on the splenocytes. It was demonstrated that IDO and NO restrained BCG-induced polarization and conversely COG-2 promoted BCG-induced pro-inflammatory polarization of MSC.Conclusions. 1. MSC actively participate in the formation of immunologic anti-mycobacterial resistance. 2. Targeted regulation of IDO and NO production can be feasibly applied for formation of anti-tuberculous vaccinal immunity and control mycobacterial infection.
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spelling doaj.art-29bc732e3df7466dbaa6319b5eeaa7f12023-09-03T08:57:17ZrusNew Terra Publishing HouseТуберкулез и болезни лёгких2075-12302542-15062016-11-019411566210.21292/2075-1230-2016-94-11-56-62957BCG-INDUCED PRO-INFLAMMATORY PHENOTYPE OF MESENCHYMAL STEM CELLS: EFFECT OF IMMUNE MODULATORSA. Sh. Shvarts0S. N. Belogorodtsev1A. E. Petrenko2L. O. Degtyareva3A. I. Shakhmuradova4ФГБУ «Новосибирский НИИ туберкулеза» Минздрава России; ФГБНУ «НИИ терапии и профилактической медицины»ФГБУ «Новосибирский НИИ туберкулеза» Минздрава России; ФГБНУ «НИИ фундаментальной и клинической иммунологии»ФГБУ «Новосибирский НИИ туберкулеза» Минздрава РоссииФГБНУ «НИИ терапии и профилактической медицины»ФГБНУ «НИИ терапии и профилактической медицины»In case of mycobacterial infection the granulomatous infiltration foci contain the significant amount of mesenchymal stem cells (MSC), which functional phenotype and respective function in anti-tuberculosis immune defense remain unknown.Goal of the study: to characterize the MSC phenotype, formed by their interaction with BCG of M. bovis and to evaluate the changes in this phenotype caused by the action of inhibitors and stimulants of immune regulatory action.Materials and methods: MSC retrieved from bone marrow of mice were cultured with the presence and absence of BCG of M. bovis and/or poludanum TLR3 agonist; and the effect of two latter on the production of pro- and anti-inflammatory cytokines was evaluated by enzyme multiplied immunoassay. Flow cytometry and radioactive testing were used to evaluate the impact of cultured BCG fluid and poludanum-conditioned MSC on the proliferative and apoptotic activity of splenocytes. The inhibitors of indoleamine 2,3-dioxygenase (IDO), cyclooxygenase-2 (COG-2) or NO synthase were added to certain cultures alone with BCG and poludanum, and the contributions of IDO, COG-2 and NO to BCG and poludanum-induced response were assessed.Results. Pro-inflammatory polarization of MSC under the action of BCG and poludanum was demonstrated. Pro-inflammatory MSC phenotype correlated to their anti-apoptogenic and growth-stimulating actions on the splenocytes. It was demonstrated that IDO and NO restrained BCG-induced polarization and conversely COG-2 promoted BCG-induced pro-inflammatory polarization of MSC.Conclusions. 1. MSC actively participate in the formation of immunologic anti-mycobacterial resistance. 2. Targeted regulation of IDO and NO production can be feasibly applied for formation of anti-tuberculous vaccinal immunity and control mycobacterial infection.https://www.tibl-journal.com/jour/article/view/957мезенхимальные стволовые клеткибцжполуданцитокиныоксид азотациклооксигеназа-2индоламин-2
spellingShingle A. Sh. Shvarts
S. N. Belogorodtsev
A. E. Petrenko
L. O. Degtyareva
A. I. Shakhmuradova
BCG-INDUCED PRO-INFLAMMATORY PHENOTYPE OF MESENCHYMAL STEM CELLS: EFFECT OF IMMUNE MODULATORS
Туберкулез и болезни лёгких
мезенхимальные стволовые клетки
бцж
полудан
цитокины
оксид азота
циклооксигеназа-2
индоламин-2
title BCG-INDUCED PRO-INFLAMMATORY PHENOTYPE OF MESENCHYMAL STEM CELLS: EFFECT OF IMMUNE MODULATORS
title_full BCG-INDUCED PRO-INFLAMMATORY PHENOTYPE OF MESENCHYMAL STEM CELLS: EFFECT OF IMMUNE MODULATORS
title_fullStr BCG-INDUCED PRO-INFLAMMATORY PHENOTYPE OF MESENCHYMAL STEM CELLS: EFFECT OF IMMUNE MODULATORS
title_full_unstemmed BCG-INDUCED PRO-INFLAMMATORY PHENOTYPE OF MESENCHYMAL STEM CELLS: EFFECT OF IMMUNE MODULATORS
title_short BCG-INDUCED PRO-INFLAMMATORY PHENOTYPE OF MESENCHYMAL STEM CELLS: EFFECT OF IMMUNE MODULATORS
title_sort bcg induced pro inflammatory phenotype of mesenchymal stem cells effect of immune modulators
topic мезенхимальные стволовые клетки
бцж
полудан
цитокины
оксид азота
циклооксигеназа-2
индоламин-2
url https://www.tibl-journal.com/jour/article/view/957
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AT snbelogorodtsev bcginducedproinflammatoryphenotypeofmesenchymalstemcellseffectofimmunemodulators
AT aepetrenko bcginducedproinflammatoryphenotypeofmesenchymalstemcellseffectofimmunemodulators
AT lodegtyareva bcginducedproinflammatoryphenotypeofmesenchymalstemcellseffectofimmunemodulators
AT aishakhmuradova bcginducedproinflammatoryphenotypeofmesenchymalstemcellseffectofimmunemodulators