Toll-like receptor 3 regulates cord blood-derived endothelial cell function in vitro and in vivo

Autor: Nicole Balitrand, Jérôme Larghero, Jean-Pierre Marolleau, Séverine Lecourt, Yves Lepelletier, Delphine Freida, Hélène Riesterer, Catherine Delmau, Marie-Caroline Lebousse-Kerdiles, Georges Uzan, Aurore Grelier, Wendy Cuccini, Valérie Vanneaux, Jean-Jacques Lataillade, Régis Peffault de Latour, Audrey Cras
Přispěvatelé: Unité de Thérapie Cellulaire, Hopital St Louis, Cytokines, hématopoïèse et réponse immune (CHRI), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Laboratoire de Biologie à Grande Échelle (BGE - UMR S1038), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Grenoble Alpes (UGA)-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Hôpital d'instruction des Armées Percy, Service de Santé des Armées, CHU Saint Louis [APHP], Service clinique des Maladies du Sang, Hopital d'Amiens, Microenvironnement et Physiopathologie de la Differenciation, Université Paris-Sud - Paris 11 (UP11)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de pharmacie, Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Université Paris Descartes - Paris 5 (UPD5)-CHU Necker - Enfants Malades [AP-HP], Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Hopital Saint-Louis [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), CHU Amiens-Picardie, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Descartes - Paris 5 (UPD5)-CHU Necker - Enfants Malades [AP-HP], Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])
Rok vydání: 2012
Předmět:
Cancer Research
Physiology
Angiogenesis
[SDV]Life Sciences [q-bio]
Clinical Biochemistry
Oligonucleotides
Mice
SCID
Systemic inflammation
Ligands
Mice
0302 clinical medicine
Cell Movement
Ischemia
Mice
Inbred NOD
ComputingMilieux_MISCELLANEOUS
Cells
Cultured
0303 health sciences
Toll-like receptor
Cell Cycle
Toll-Like Receptors
Cell cycle
Fetal Blood
3. Good health
Cell biology
Hindlimb
Endothelial stem cell
Lipoproteins
LDL
030220 oncology & carcinogenesis
Cord blood
Cytokines
Female
medicine.symptom
Cell Division
Neovascularization
Physiologic
Biology
Mesenchymal Stem Cell Transplantation
Real-Time Polymerase Chain Reaction
03 medical and health sciences
medicine
Animals
Humans
Progenitor cell
030304 developmental biology
Wound Healing
Cell growth
Tumor Necrosis Factor-alpha
Infant
Newborn
Endothelial Cells
Mesenchymal Stem Cells
Toll-Like Receptor 3
MicroRNAs
Poly I-C
Gene Expression Regulation
Endothelium
Vascular
Zdroj: Angiogenesis
Angiogenesis, Springer Verlag, 2013, 16 (4), pp.821-836. ⟨10.1007/s10456-013-9358-5⟩
Angiogenesis, 2013, 16 (4), pp.821-836. ⟨10.1007/s10456-013-9358-5⟩
ISSN: 1573-7209
0969-6970
DOI: 10.1007/s10456-013-9358-5⟩
Popis: Circulating endothelial progenitor cells (cEPC) are capable of homing to neovascularisation sites, in which they proliferate and differentiate into endothelial cells. Transplantation of cEPC-derived cells, in particular those isolated from umbilical cord blood (UCB), has emerged as a promising approach in the treatment of cardio-vascular diseases. After in vivo transplantation, these cells may be exposed to local or systemic inflammation or pathogens, of which they are a common target. Because Toll-like receptors (TLR) are critical in detecting pathogens and in initiating inflammatory responses, we hypothesized that TLR may govern UCB cEPC-derived cells function. While these cells expressed almost all TLR, we found that only TLR3 dramatically impaired cell properties. TLR3 activation inhibited cell proliferation, modified cell cycle entry, impaired the in vitro angiogenic properties and induced pro-inflammatory cytokines production. The anti-angiogenic effect of TLR3 activation was confirmed in vivo in a hind-limb ischemic mice model. Moreover, TLR3 activation consistently leads to an upregulation of miR-29b, -146a and -155 and to a deregulation of cytoskeleton and cell cycle regulator. Hence, TLR3 activation is likely to be a key regulator of cEPC-derived cells properties.
Databáze: OpenAIRE
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