Toll-Like Receptor 2- and 6-Mediated Stimulation by Macrophage-Activating Lipopeptide 2 Induces Lipopolysaccharide (LPS) Cross Tolerance in Mice, Which Results in Protection from Tumor Necrosis Factor Alpha but in Only Partial Protection from Lethal LPS Doses

Deiters, Ursula; Gumenscheimer, Marina; Galanos, Chris; Mühlradt, Peter F.

doi:10.1128/iai.71.8.4456-4462.2003

Cited by 41 publications

(50 citation statements)

References 61 publications

(54 reference statements)

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“…MALP-2 is so far one of the few definitely identified natural ligands signalling via this pathway. Of note, MALP-2 also exhibits a remarkable therapeutic potential and has been successfully used in different experimental and even clinical studies, ranging from dermal wound healing to anti-tumour treatment (Rharbaoui et al, 2002;Deiters et al, 2003;Schneider et al, 2004;Schmidt et al, 2007). Of note, we uncovered a tissue regenerative capacity of MALP-2.…”

Section: Discussionmentioning

confidence: 70%

“…Of note, MALP-2 is synthetically available and has been already used in multiple studies. MALP-2 stimulation of the immune response has potential therapeutic implications, e.g., as a mucosal adjuvant for vaccination (Rharbaoui et al, 2002) or to induce lipopolysaccharide cross tolerance (Deiters et al, 2003). In oncology, intratumoural application of MALP-2 leads to significant tumour suppression in mice with pancreatic cancer (Schneider et al, 2004).…”

Section: Introductionmentioning

confidence: 99%

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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: 70%

Section: Introductionmentioning

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

View full text Add to dashboard Cite

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“…The crucial requirement for TNF for optimal innate immune defense against bacterial infections has been documented in many models (7,30). Enhanced resistance to bacterial infection can be induced by pretreatment with TNF, supporting the idea of TNF participating in LPS-induced tolerance (4,26). Also, TNF seems to initiate the appropriate inflammatory reaction early at the onset of infection (16).…”

mentioning

confidence: 91%

Divergence of Protection Induced by Bacterial Products and Sepsis-Induced Immune Suppression

et al. 2005

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Susceptibility to bacterial infections after a primary immune stimulation differs drastically depending on the presensitization of the innate immune system. To determine the conditions that either induce protection or enhanced susceptibility to infection with Salmonella enterica serovar Typhimurium, we pretreated mice either with tumor necrosis factor (TNF), whole killed bacteria, or sublethal cecal ligation and puncture (CLP) as a mouse model for septic peritonitis. Impaired production of the cytokines TNF, interleukin-6 (IL-6), and IL-10 was induced by these pretreatment schedules, with TNF-signaling not being essential for this effect. Injection of TNF or killed bacteria enhanced survival of mice infected subsequently with serovar Typhimurium. In contrast, sepsis such as that induced by CLP only protected from shock induced by D-galactosamine and lipopolysaccharide or by a high dose of bacteria but sensitized to a secondary bacterial infection. Such sepsis-induced enhanced susceptibility to infection was critically dependent on TNF function.

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“…Moreover, Rushworth et al reported that LPS-dependent HO-1 protein expression was undetectable within 8 h (4), a result that differed from our study. This difference may be due to differences in recognition receptors, i.e., monocytes recognize MALP-2 by TLR2 and -6, but this process is partially dependent on CD14, while TLR4 and CD14 are required for LPS (32,33).…”

Section: Discussionmentioning

confidence: 99%

Mycoplasma fermentans MALP-2 Induces Heme Oxygenase-1 Expression via Mitogen-Activated Protein Kinases and Nrf2 Pathways To Modulate Cyclooxygenase 2 Expression in Human Monocytes

You

Zeng

et al. 2013

Clin Vaccine Immunol

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Toll-Like Receptor 2- and 6-Mediated Stimulation by Macrophage-Activating Lipopeptide 2 Induces Lipopolysaccharide (LPS) Cross Tolerance in Mice, Which Results in Protection from Tumor Necrosis Factor Alpha but in Only Partial Protection from Lethal LPS Doses

Cited by 41 publications

References 61 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

Divergence of Protection Induced by Bacterial Products and Sepsis-Induced Immune Suppression

Mycoplasma fermentans MALP-2 Induces Heme Oxygenase-1 Expression via Mitogen-Activated Protein Kinases and Nrf2 Pathways To Modulate Cyclooxygenase 2 Expression in Human Monocytes

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