Chromosomal Localization ofTIL,a Gene Encoding a Protein Related to theDrosophilaTransmembrane Receptor Toll, to Human Chromosome 4p14

Taguchi, Takahiro; Mitcham, Jennifer L.; Dower, Steven K.; Sims, John E.; Testa, Joseph R.

doi:10.1006/geno.1996.0150

Cited by 95 publications

(41 citation statements)

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“…Mammalian TLRs are homologues of the Drosophila Toll protein and were discovered in the mid-90s of the last TLR2/6 stimulation of MSCs promotes angiogenesis century (Taguchi et al, 1996;Medzhitov et al, 1997). Initially, they were exclusively considered as sentinels of the immune system in order to organise the body´s pathogen defence in response to PAMPs of bacterial and viral origin by the activation of classical inflammatory signalling pathways such as the mitogen-activated protein kinase (MAPK) cascade or nuclear factor-κB (NF-κB) (Brown et al, 2011).…”

Section: Discussionmentioning

confidence: 99%

Toll-like receptor 2/6-dependent stimulation of mesenchymal stem cells promotes angiogenesis by paracrine factors

Grote

Petri²,

Liu³

et al. 2013

eCM

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Reconstruction of critical size bone defects represents a major challenge in orthopaedic surgery. Insufficient angiogenesis is a limiting factor for engraftment of largescale tissue transplants. Transplantation or stimulation of local mesenchymal stem cells (MSCs) represents a potential solution to enhance angiogenesis. We recently identified angiogenic properties for the Toll-like receptor (TLR) 2/6 agonist MALP-2 and now investigated if MALP-2 could be used to stimulate MSCs in order to promote angiogenesis in vitro and in vivo.Human MSCs from the bone marrow of healthy subjects were isolated, cultured and expanded in vitro and were shown to be positive for mesenchymal stem cells markers as well as for the MALP-2 receptors TLR2 and TLR6. MALP-2 directly enhanced migration but not proliferation of human MSCs. Conditioned medium from MALP-2 stimulated MSCs significantly increased proliferation, migration and tube formation of endothelial cells. Analysis of the conditioned medium from MSCs revealed that MALP-2 stimulation enhanced the secretion of several chemokines and growth factors including vascular endothelial growth factors (VEGF) and granulocytemacrophage colony-stimulating factor (GM-CSF). Finally, we studied MALP-2 effects on MSCs in a sheep model of tissue engineering in vivo. Therefore, MSCs were isolated from the iliac crest of black head sheep and co-cultivated with MALP-2 ex vivo. Implantation of autologous MSCs within a scaffold cylinder into the M. latissimus dorsi significantly enhanced vessel density of these constructs after 6 months.We here present the first evidence that TLR2/6-dependent stimulation of MSCs promotes angiogenesis in vitro and in vivo offering a novel strategy for therapeutic angiogenesis, e.g., for tissue engineering of bone.

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Section: Discussionmentioning

confidence: 99%

Toll-like receptor 2/6-dependent stimulation of mesenchymal stem cells promotes angiogenesis by paracrine factors

Grote

Petri²,

Liu³

et al. 2013

eCM

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“…In addition to controlling certain developmental processes, toll mediates immunity in flies to fungal and Gram-positive bacteria infections (Gay & Keith 1991, Belvin & Anderson 1996, Lemaitre et al 1996, Imler & Hoffmann 2001 and was noted to share certain homology with the human IL-1 receptor (Gay & Keith 1991). In the mid-1990s, the field of Toll biology moved beyond flies when several groups identified areas in mammalian gene sequences encoding proteins homologous to toll (Taguchi et al 1996, Medzhitov et al 1997, Rock et al 1998. In another seminal publication, Medzhitov et al (1997) showed that activation of a human TLR leads to activation of transcription factor NFkB and elements of innate immune responses (Medzhitov et al 1997).…”

Section: Identification and Elucidation Of The Role Of Tlr4mentioning

confidence: 99%

Critical role of toll-like receptors and nucleotide oligomerisation domain in the regulation of health and disease

Mitchell¹,

Paul-Clark²,

Clarke³

et al. 2007

Journal of Endocrinology

118

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Pathogens are sensed by pattern recognition receptors (PRRs), which are germ line-encoded receptors, including transmembrane Toll-like receptors (TLRs) and cytosolic nucleotide oligomerisation domain (NOD) proteins, containing leucine-rich repeats (NLRs). Activation of PRRs by specific pathogen-associated molecular patterns (PAMPs) results in genomic responses in host cells involving activation transcription factors and the induction of genes. There are now at least 10 TLRs in humans and 13 in mice, and 2 NLRs (NOD1 and NOD2). TLR signalling is via interactions with adaptor proteins including MyD88 and tollreceptor associated activator of interferon (TRIF). NOD signalling is via the inflammasome and involves activation of Rip-like interactive clarp kinase (RICK). Bacterial lipopolysaccharide (LPS) from Gram-negative bacteria is the beststudied PAMP and is activated by or 'sensed' by TLR4. Lipoteichoic acid (LTA) from Gram-positive bacteria is sensed by TLR2. TLR4 and TLR2 have different signalling cascades, although activation of either results in symptoms of sepsis and shock. This review describes the rapidly expanding field of pathogen-sensing receptors and uses LPS and LTA as examples of how these pathways parallel and diverge from each other. The role of pathogen-sensing pathways in disease is also discussed.

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“…The uncovering of hTLRs, of which two have been published to date [14,15] and a further three are in the database, is of some interest. Janeway et al [15] have indicated that hToll (hTLR4) may be critical for innate immunity and have provided evidence for hTLR4 as being a trigger for macrophage activation.…”

Section: Human Toll-like Receptors (Htlrs) and Innate Immunitymentioning

confidence: 99%

Signal transduction pathways activated by the IL-1 receptor family: ancient signaling machinery in mammals, insects, and plants

O’Neill

Greene

1998

Journal of Leukocyte Biology

524

345

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Chromosomal Localization ofTIL,a Gene Encoding a Protein Related to theDrosophilaTransmembrane Receptor Toll, to Human Chromosome 4p14

Cited by 95 publications

References 0 publications

Toll-like receptor 2/6-dependent stimulation of mesenchymal stem cells promotes angiogenesis by paracrine factors

Toll-like receptor 2/6-dependent stimulation of mesenchymal stem cells promotes angiogenesis by paracrine factors

Critical role of toll-like receptors and nucleotide oligomerisation domain in the regulation of health and disease

Signal transduction pathways activated by the IL-1 receptor family: ancient signaling machinery in mammals, insects, and plants

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