Transcriptional Profile of Cytokines, Regulatory Mediators and TLR in Mesenchymal Stromal Cells after Inflammatory Signaling and Cell-Passaging

Makram Merimi; Karolien Buyl; Dhouha Daassi; Robim M Rodrigues; Rahma Melki; Philippe Lewalle; Tamara Vanhaecke; Hassan Fahmi; Vera Rogiers; Laurence Lagneaux; Joery De Kock; Mehdi Najar

doi:10.3390/ijms22147309

Transcriptional Profile of Cytokines, Regulatory Mediators and TLR in Mesenchymal Stromal Cells after Inflammatory Signaling and Cell-Passaging

Makram Merimi, Karolien Buyl, Dhouha Daassi, Robim M Rodrigues, Rahma Melki, Philippe Lewalle, Tamara Vanhaecke, Hassan Fahmi, Vera Rogiers, Laurence Lagneaux, Joery De Kock, Mehdi Najar

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Abstract

Adult human subcutaneous adipose tissue (AT) harbors a rich population of mesenchymal stromal cells (MSCs) that are of interest for tissue repair. For this purpose, it is of utmost importance to determine the response of AT-MSCs to proliferative and inflammatory signals within the damaged tissue. We have characterized the transcriptional profile of cytokines, regulatory mediators and Toll-like receptors (TLR) relevant to the response of MSCs. AT-MSCs constitutively present a distinct profile for each gene and differentially responded to inflammation and cell-passaging. Inflammation leads to an upregulation of IL-6, IL-8, IL-1β, TNFα and CCL5 cytokine expression. Inflammation and cell-passaging increased the expression of HGF, IDO1, PTGS1, PTGS2 and TGFβ. The expression of the TLR pattern was differentially modulated with TLR 1, 2, 3, 4, 9 and 10 being increased, whereas TLR 5 and 6 downregulated. Functional enrichment analysis demonstrated a complex interplay between cytokines, TLR and regulatory mediators central for tissue repair. This profiling highlights that following a combination of inflammatory and proliferative signals, the sensitivity and responsive capacity of AT-MSCs may be significantly modified. Understanding these transcriptional changes may help the development of novel therapeutic approaches.

Original language	English
Article number	7309
Number of pages	24
Journal	International Journal of Molecular Sciences
Volume	22
Issue number	14
DOIs	https://doi.org/10.3390/ijms22147309 https://doi.org/10.3390/ijms22147309
Publication status	Published - 7 Jul 2021

Bibliographical note

Funding Information:
Funding: This research has received funding from grants of Generations For Life Foundation, the Scientific Research Foundation Flanders (FWO), Le Fonds National de la Recherche Scientifique (FRSM, Télévie), Research Project (PDR) grant (35036908), Les Amis de l’Institut Bordet, the Arthritis Society (SOG-20-0000000046), the Canadian Institutes of Health Research (PTJ175110), the Research Council (OZR) of the Vrije Universiteit Brussel (VUB) and the Inter-university Attraction Pole programme of the Belgian Science Policy Office (IAP-HEPRO BELSPO).

Publisher Copyright:
© 2021 by the authors. Licensee MDPI, Basel, Switzerland.

Copyright:
Copyright 2022 Elsevier B.V., All rights reserved.

Keywords

Cell Proliferation/genetics
Cytokines/genetics
Down-Regulation/genetics
Gene Expression Regulation/genetics
Humans
Inflammation/genetics
Mesenchymal Stem Cells/metabolism
Signal Transduction/genetics
Subcutaneous Fat/metabolism
Toll-Like Receptors/genetics
Transcription, Genetic/genetics
Up-Regulation/genetics

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Merimi, M., Buyl, K., Daassi, D., Rodrigues, R. M., Melki, R., Lewalle, P., Vanhaecke, T., Fahmi, H., Rogiers, V., Lagneaux, L., De Kock, J., & Najar, M. (2021). Transcriptional Profile of Cytokines, Regulatory Mediators and TLR in Mesenchymal Stromal Cells after Inflammatory Signaling and Cell-Passaging. International Journal of Molecular Sciences, 22(14), Article 7309. https://doi.org/10.3390/ijms22147309, https://doi.org/10.3390/ijms22147309

@article{519836543a914913937aef99427ee89b,

title = "Transcriptional Profile of Cytokines, Regulatory Mediators and TLR in Mesenchymal Stromal Cells after Inflammatory Signaling and Cell-Passaging",

abstract = "Adult human subcutaneous adipose tissue (AT) harbors a rich population of mesenchymal stromal cells (MSCs) that are of interest for tissue repair. For this purpose, it is of utmost importance to determine the response of AT-MSCs to proliferative and inflammatory signals within the damaged tissue. We have characterized the transcriptional profile of cytokines, regulatory mediators and Toll-like receptors (TLR) relevant to the response of MSCs. AT-MSCs constitutively present a distinct profile for each gene and differentially responded to inflammation and cell-passaging. Inflammation leads to an upregulation of IL-6, IL-8, IL-1β, TNFα and CCL5 cytokine expression. Inflammation and cell-passaging increased the expression of HGF, IDO1, PTGS1, PTGS2 and TGFβ. The expression of the TLR pattern was differentially modulated with TLR 1, 2, 3, 4, 9 and 10 being increased, whereas TLR 5 and 6 downregulated. Functional enrichment analysis demonstrated a complex interplay between cytokines, TLR and regulatory mediators central for tissue repair. This profiling highlights that following a combination of inflammatory and proliferative signals, the sensitivity and responsive capacity of AT-MSCs may be significantly modified. Understanding these transcriptional changes may help the development of novel therapeutic approaches.",

keywords = "Cell Proliferation/genetics, Cytokines/genetics, Down-Regulation/genetics, Gene Expression Regulation/genetics, Humans, Inflammation/genetics, Mesenchymal Stem Cells/metabolism, Signal Transduction/genetics, Subcutaneous Fat/metabolism, Toll-Like Receptors/genetics, Transcription, Genetic/genetics, Up-Regulation/genetics",

author = "Makram Merimi and Karolien Buyl and Dhouha Daassi and Rodrigues, {Robim M} and Rahma Melki and Philippe Lewalle and Tamara Vanhaecke and Hassan Fahmi and Vera Rogiers and Laurence Lagneaux and {De Kock}, Joery and Mehdi Najar",

note = "Funding Information: Funding: This research has received funding from grants of Generations For Life Foundation, the Scientific Research Foundation Flanders (FWO), Le Fonds National de la Recherche Scientifique (FRSM, T{\'e}l{\'e}vie), Research Project (PDR) grant (35036908), Les Amis de l{\textquoteright}Institut Bordet, the Arthritis Society (SOG-20-0000000046), the Canadian Institutes of Health Research (PTJ175110), the Research Council (OZR) of the Vrije Universiteit Brussel (VUB) and the Inter-university Attraction Pole programme of the Belgian Science Policy Office (IAP-HEPRO BELSPO). Publisher Copyright: {\textcopyright} 2021 by the authors. Licensee MDPI, Basel, Switzerland. Copyright: Copyright 2022 Elsevier B.V., All rights reserved.",

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language = "English",

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Merimi, M, Buyl, K, Daassi, D, Rodrigues, RM, Melki, R, Lewalle, P, Vanhaecke, T, Fahmi, H, Rogiers, V, Lagneaux, L, De Kock, J & Najar, M 2021, 'Transcriptional Profile of Cytokines, Regulatory Mediators and TLR in Mesenchymal Stromal Cells after Inflammatory Signaling and Cell-Passaging', International Journal of Molecular Sciences, vol. 22, no. 14, 7309. https://doi.org/10.3390/ijms22147309, https://doi.org/10.3390/ijms22147309

TY - JOUR

T1 - Transcriptional Profile of Cytokines, Regulatory Mediators and TLR in Mesenchymal Stromal Cells after Inflammatory Signaling and Cell-Passaging

AU - Merimi, Makram

AU - Buyl, Karolien

AU - Daassi, Dhouha

AU - Rodrigues, Robim M

AU - Melki, Rahma

AU - Lewalle, Philippe

AU - Vanhaecke, Tamara

AU - Fahmi, Hassan

AU - Rogiers, Vera

AU - Lagneaux, Laurence

AU - De Kock, Joery

AU - Najar, Mehdi

N1 - Funding Information: Funding: This research has received funding from grants of Generations For Life Foundation, the Scientific Research Foundation Flanders (FWO), Le Fonds National de la Recherche Scientifique (FRSM, Télévie), Research Project (PDR) grant (35036908), Les Amis de l’Institut Bordet, the Arthritis Society (SOG-20-0000000046), the Canadian Institutes of Health Research (PTJ175110), the Research Council (OZR) of the Vrije Universiteit Brussel (VUB) and the Inter-university Attraction Pole programme of the Belgian Science Policy Office (IAP-HEPRO BELSPO). Publisher Copyright: © 2021 by the authors. Licensee MDPI, Basel, Switzerland. Copyright: Copyright 2022 Elsevier B.V., All rights reserved.

PY - 2021/7/7

Y1 - 2021/7/7

N2 - Adult human subcutaneous adipose tissue (AT) harbors a rich population of mesenchymal stromal cells (MSCs) that are of interest for tissue repair. For this purpose, it is of utmost importance to determine the response of AT-MSCs to proliferative and inflammatory signals within the damaged tissue. We have characterized the transcriptional profile of cytokines, regulatory mediators and Toll-like receptors (TLR) relevant to the response of MSCs. AT-MSCs constitutively present a distinct profile for each gene and differentially responded to inflammation and cell-passaging. Inflammation leads to an upregulation of IL-6, IL-8, IL-1β, TNFα and CCL5 cytokine expression. Inflammation and cell-passaging increased the expression of HGF, IDO1, PTGS1, PTGS2 and TGFβ. The expression of the TLR pattern was differentially modulated with TLR 1, 2, 3, 4, 9 and 10 being increased, whereas TLR 5 and 6 downregulated. Functional enrichment analysis demonstrated a complex interplay between cytokines, TLR and regulatory mediators central for tissue repair. This profiling highlights that following a combination of inflammatory and proliferative signals, the sensitivity and responsive capacity of AT-MSCs may be significantly modified. Understanding these transcriptional changes may help the development of novel therapeutic approaches.

AB - Adult human subcutaneous adipose tissue (AT) harbors a rich population of mesenchymal stromal cells (MSCs) that are of interest for tissue repair. For this purpose, it is of utmost importance to determine the response of AT-MSCs to proliferative and inflammatory signals within the damaged tissue. We have characterized the transcriptional profile of cytokines, regulatory mediators and Toll-like receptors (TLR) relevant to the response of MSCs. AT-MSCs constitutively present a distinct profile for each gene and differentially responded to inflammation and cell-passaging. Inflammation leads to an upregulation of IL-6, IL-8, IL-1β, TNFα and CCL5 cytokine expression. Inflammation and cell-passaging increased the expression of HGF, IDO1, PTGS1, PTGS2 and TGFβ. The expression of the TLR pattern was differentially modulated with TLR 1, 2, 3, 4, 9 and 10 being increased, whereas TLR 5 and 6 downregulated. Functional enrichment analysis demonstrated a complex interplay between cytokines, TLR and regulatory mediators central for tissue repair. This profiling highlights that following a combination of inflammatory and proliferative signals, the sensitivity and responsive capacity of AT-MSCs may be significantly modified. Understanding these transcriptional changes may help the development of novel therapeutic approaches.

KW - Cell Proliferation/genetics

KW - Cytokines/genetics

KW - Down-Regulation/genetics

KW - Gene Expression Regulation/genetics

KW - Humans

KW - Inflammation/genetics

KW - Mesenchymal Stem Cells/metabolism

KW - Signal Transduction/genetics

KW - Subcutaneous Fat/metabolism

KW - Toll-Like Receptors/genetics

KW - Transcription, Genetic/genetics

KW - Up-Regulation/genetics

UR - http://www.scopus.com/inward/record.url?scp=85109065868&partnerID=8YFLogxK

U2 - 10.3390/ijms22147309

DO - 10.3390/ijms22147309

M3 - Article

C2 - 34298927

SN - 1661-6596

VL - 22

JO - International Journal of Molecular Sciences

JF - International Journal of Molecular Sciences

IS - 14

M1 - 7309

ER -

Transcriptional Profile of Cytokines, Regulatory Mediators and TLR in Mesenchymal Stromal Cells after Inflammatory Signaling and Cell-Passaging

Abstract

Bibliographical note

Keywords

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