Human Skin Endothelial Cells Can Express All 10<i>TLR</i>Genes and Respond to Respective Ligands

Fitzner, Nicole; Clauberg, Sigrid; Eßmann, Frank; Liebmann, J.; Kolb-Bachofen, Victoria

doi:10.1128/cvi.00257-07

Cited by 98 publications

(86 citation statements)

References 24 publications

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“…The ligand of this complex is however not yet known. TLR1 is ubiquitously expressed in leukocytes but is also found in non-immune cells such as astrocytes, fibroblasts, keratinocytes (45), endothelial (46) and epithelial cells (47). (53-55), and it was suggested that TLR2 might play a role in the response to infection with viruses from the herpes family (56)(57)(58).…”

Section: Toll-like Receptors In Detailmentioning

confidence: 99%

TLRs and chronic inflammation

Ospelt

Gay

2010

The International Journal of Biochemistry & Cell Biology

156

127

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After the discovery of Toll-like receptors (TLRs), innate immune mechanisms came back in the focus of scientific research. With more and more mechanisms of TLR biology known, it has become clear that these and also other innate immune receptors are not only of crucial importance in the immune response to invading pathogens, but also play a role in the homeostasis of commensal flora and in the response to stress and danger signals. In this respect, increasing evidence is found that inappropriate quantity or quality of TLR ligands or aberrant response to TLR activation plays a role in a variety of chronic inflammatory diseases. In this review, an overview of the currently known TLRs and their signaling pathways is given and reports about their expression and activation in chronic inflammatory diseases are recapitulated. TLRs and chronic inflammation Abstract:After the discovery of Toll-like receptors (TLRs), innate immune mechanisms came back in the focus of scientific research. With more and more mechanisms of TLR biology known, it has become clear that these and also other innate immune receptors are not only of crucial importance in the immune response to invading pathogens, but also play a role in the homeostasis of commensal flora and in the response to stress and danger signals. In this respect, increasing evidence is found that inappropriate quantity or quality of TLR ligands or aberrant response to TLR activation plays a role in a variety of chronic inflammatory diseases.In this review, an overview of the currently known TLRs and their signaling pathways isgiven and reports about their expression and activation in chronic inflammatory diseases are recapitulated.2

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Section: Toll-like Receptors In Detailmentioning

confidence: 99%

TLRs and chronic inflammation

Ospelt

Gay

2010

The International Journal of Biochemistry & Cell Biology

156

127

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“…When a highly purified LTA preparation became available [7], LTA was shown to induce the production of proinflammatory cytokines by human monocytes and murine macrophages by interacting with the heterodimer TLR2 and TLR6 [8,9], but not leukocyte recruitment to human microvascular endothelial cells in vitro [10] or in the murine microvasculature in vivo [10,11]. Further studies suggest that the proinflammatory response to TLR ligands by human arterial and venular endothelial cells or cell lines requires priming by inflammatory mediators such as IFN-g [12][13][14]. LTA-induced Weibel-Palade body exocytosis in aortic endothelial cells with release of von Willebrand factor and P-selectin was also enhanced by IFN-g priming [15].…”

Section: Introductionmentioning

confidence: 99%

Divergent roles of Toll‐like receptor 2 in response to lipoteichoic acid and Staphylococcus aureus in vivo

et al. 2010

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The response of leukocytes to lipoteichoic acid (LTA), a TLR2-dependent major cell wall component of Staphylococcus aureus, is linked to the outcome of an infection. In this study we investigated the role of nonhematopoietic TLR2 in response to LTA and S. aureus by creating bone marrow chimeras. Significant leukocyte recruitment in response to LTA required IFN-c priming in WT C57BL/6 and TLR2 À/À ) WT mice, but was not observed in TLR2 À/À or WT ) TLR2 À/À animals. LTA also induced a proinflammatory response in IFN-c primed primary human microvascular endothelial cells leading to leukocyte recruitment in vitro. When mice were infected with S. aureus, the most profound elevation of TNF-a and IL-6 was seen in TLR2 À/À and TLR2 À/À ) WT mice. TLR2 À/À , but not chimeric mice, demonstrated increased IL-17, blood leukocytosis and pulmonary neutrophilia compared to WT mice. Collectively, the results suggest an essential role for IFN-c and nonhematopoietic TLR2 for leukocyte recruitment in response to LTA. In contrast, TLR2 on both hematopoietic and nonhematopoietic cells appears to orchestrate an inhibitory response to S. aureus such that in complete TLR2 deficiency, there is an exaggerated proinflammatory response and/or skewing of the immune response towards a Th17 phenotype that may contribute to the decreased survival of TLR2 À/À mice. Key words: Endothelial cells . Leukocyte recruitment . Lipoteichoic acidStaphyloccoccus aureus . TLR2 IntroductionStaphyloccoccus aureus is the most common causative agent of bacteremia in the Western world and is associated with high mortality. Despite the increasing importance of S. aureus infection, how the pathogen is recognized by the innate immune system in vivo remains incompletely understood. S. aureus possesses a number of PAMP that may activate the host innate immune system [1]. These PAMP include peptidoglycan (PGN), lipoteichoic acid (LTA), lipoproteins and unmethylated CpG DNA. PGN is recognized by the peptidoglyan recognizing proteins and the PGN subcomponent muramyl dipeptide (MDP) is recognized by the cytosolic sensor nucleotide-binding oligomerization domain 2 (NOD2). S. aureus LTA and lipoproteins are recognized by TLR2. CpG DNA is recognized by TLR9. The strongest evidence to date suggests that both TLR2 and NOD, Eur. J. Immunol. 2010. 40: 1639-1650 DOI 10.1002 Immunity to infection 1639 possibly in concert, facilitate innate immune recognition of S. aureus [2][3][4][5]. However the in vivo importance of each PAMP from S. aureus in driving the innate immune response and the target cells each acts on has not been clearly elucidated. The important role of TLR2 in host defense against S. aureus has long been established. An intravenous inoculum of 10 7 organisms resulted in 90% mortality by day 14 in TLR2-deficient mice, compared to 40% in WT animals [2]. A larger inoculum (10 8 cfu) resulted in 100% mortality by day 5 [3]. Mortality in TLR2 À/À mice was correlated with the inhibition of TNF-a production by peritoneal macrophages in response to LTA, a major cell wal...

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“…Endothelial cells also express TLR4 (6). Therefore, endothelial cells can respond to TLR4 ligands, and release proinflammatory factors.…”

Section: Discussionmentioning

confidence: 99%

“…In other experiments, B16 cells were cultured in the presence of pre-fixed cells for 48 h, and then irradiated with UVB (200 J/m 2 ) or treated with mitomycin C (MMC, 10 μg/ml) for 12 h. The apoptosis of cells were analyzed by flow cytometry. For the assay of B16 cell apoptosis in vivo, B16 cells were labeled with CFSE and injected into mice (2x10 6 per mouse) via tail vein. Five and twelve hours later, the whole blood was collected from mice.…”

Section: Methodsmentioning

confidence: 99%

“…TLR4 expressed in endothelial cells can be activated by engaging with TLR4 ligands such as LPS or high mobility group box 1 (HMGB1) (4,5). Subsequently, various inflammatory factors are induced in endothelial cells (5)(6)(7). Therefore, in parallel with the development of tumor inflammation, the phenotype and function of tumor-associated endothelial cells may be modified by TLR4 ligands.…”

Section: Introductionmentioning

confidence: 99%

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Endothelial cell-expressed Tim-3 facilitates metastasis of melanoma cells by activating the NF-κB pathway

Yuan²,

Liu³

et al. 2010

Oncol Rep

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Abstract. T cell immunoglobulin and mucin domain-3 (Tim-3)is originally recognized as a receptor of Th1 cells. We found that Tim-3 could be expressed in endothelial cells after stimulation with tumor cell-released TLR4 ligand. Tim-3 expressed by endothelial cells does not function as the receptor of galectin-9, but mediates the interaction of endothelial cells with tumor cells. The engagement of endothelial cellexpressed Tim-3 with a non-galectin 9 putative receptor on B16 melanoma cells could trigger the NF-κB signaling pathway in B16 cells. The activated NF-κB not only promoted the proliferation of B16 cells, but also enhanced apoptosis resistance of B16 cells by up-regulating Bcl-2 and Bcl-xL and down-regulating Bax. Consistently, Tim-3 facilitated the survival of B16 cells in the blood stream, arrested in the lung and following invasion, resulted in more metastatic nodules in the lung. These findings suggest that endothelial cell-expressed Tim-3 increases tumor cell metastatic potential by facilitating tumor cell intravasation, survival in blood stream and extravasation. Thus, antiinflammation or blockade of Tim-3 may contribute to the prevention of metastasis.

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Human Skin Endothelial Cells Can Express All 10TLRGenes and Respond to Respective Ligands

Cited by 98 publications

References 24 publications

TLRs and chronic inflammation

TLRs and chronic inflammation

Divergent roles of Toll‐like receptor 2 in response to lipoteichoic acid and Staphylococcus aureus in vivo

Endothelial cell-expressed Tim-3 facilitates metastasis of melanoma cells by activating the NF-κB pathway

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