Bacterial Lipopolysaccharide and IFN-γ Induce Toll-Like Receptor 2 and Toll-Like Receptor 4 Expression in Human Endothelial Cells: Role of NF-κB Activation

Faure, Emmanuelle; Thomas, Lisa S.; Xu, Helen; Medvedev, Andrei E.; Equils, Ozlem; Arditi, Moshe

doi:10.4049/jimmunol.166.3.2018

Cited by 427 publications

(317 citation statements)

References 65 publications

(55 reference statements)

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“…These have been shown to induce TLR2 specific responses measured as NFjB activation in macrophages and endothelial cells (Faure et al, 2001;Wang et al, 2000). We tested the ability of these cytokines to induce TLR2 expression by GCV-purified astrocytes.…”

Section: Tnfa and Il-1b Directly Induce Activation Of Astrocytesmentioning

confidence: 99%

Microglia are required for astroglial toll‐like receptor 4 response and for optimal TLR2 and TLR3 response

Holm

Dræby

Owens

2012

Glia

111

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Within the central nervous system, astrocytes and microglia are the primary responders to endogenous ligands released upon injury and stress, as well as to infectious pathogens. Toll-like receptors (TLRs) are implicated in recognition of both types of stimulus. Whether astrocytes respond as strongly as microglia to TLR agonists remains contentious. In this study, we have rigorously purified astrocytes to determine their capacity for autonomous TLR response, in absence of microglia. We used flow cytometry and differential adhesion as well as a myeloid lineage-specific suicide gene to purify astrocytes from mixed glial cultures and measured their response to TLR agonists. Our results show that the response of astrocytes to TLR2 and TLR3 agonists is greatly enhanced by, and response to TLR4 agonists is completely dependent on, the presence of functional microglia. In the case of the TLR4 response to lipopolysaccharide, microglia exert their effect on astrocytes at least partially through release of soluble mediators that directly activate or facilitate astrocyte responses. Our findings underline the contribution of glial crosstalk in CNS responses to injury or inflammation. V

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Section: Tnfa and Il-1b Directly Induce Activation Of Astrocytesmentioning

confidence: 99%

Microglia are required for astroglial toll‐like receptor 4 response and for optimal TLR2 and TLR3 response

Holm

Dræby

Owens

2012

Glia

111

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“…Human umbilical vein EC (HUVEC) express high levels of TLR4 and low amounts of TLR1, TLR2, and TLR6 [47,48]. Increased expression of TLR2 by EC in response to inflammatory mediators such as TNF, LPS, IL-1β, IFNγ and histamine in vivo and in vitro [49][50][51][52], however, provides a mechanism allowing EC to respond to TLR2 ligands under inflammatory conditions. TLR2 and TLR4 are both expressed on platelets [53] and on monocytes [54].…”

Section: The Role Of Members Of the Tlr Familymentioning

confidence: 99%

Receptors involved in cell activation by antiphospholipid antibodies

Brandt

Kruithof

Moerloose

2013

Thrombosis Research

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The antiphospholipid syndrome (APS) is an autoimmune disease associated with arterial or venous thrombosis and/or recurrent fetal loss and is caused by pathogenic antiphospholipid antibodies (aPLA). The plasma protein β2-glycoprotein 1 (β2GP1) has been identified as a major target of aPLA associated with APS. Cell activation by aPLA appears to be a major pathogenic cause in the pathogenesis of APS. Receptors, co-receptors and accessory molecules are known to assist the pathogenic effects of aPLA. Members of the TLR family and the platelet receptor apolipoprotein E receptor 2' (apoER2'), a receptor belonging to the low-density lipoprotein receptor (LDL-R) family, as well as GPIbα, were identified as putative candidates for aPLA recognition. CD14, a co-receptor for TLR2 and TLR4, and annexin A2, a ubiquitous Ca2+ -binding protein that is essential for actin-dependent vesicle transport, could serve as important accessory molecules in mediating the pathogenic effects of aPLA. Finally, complement activation has been reported in association with the pathogenicity of APS. The relative contribution of these different mechanisms in the pathogenesis of APS is controversial. Here, we review the various in vivo and in vitro models that have been used to investigate the pathogenic mechanisms of aPLA in APS

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Section: Introductionmentioning

confidence: 99%

“…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%

“…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]. Priming has been attributed to enhanced TLR2 expression [12] or the recruitment of intracellular TLR2 to the cell membrane [13].Paradoxically, LTA has also been shown to be anti-inflammatory in suppressing neutrophil recruitment in response to polymicrobial sepsis through the downregulation of the chemokine receptor CXCR2 on neutrophils [16]. TLR2 À/À animals showed decreased cytokine production, higher bacterial clearance and improved survival.…”

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confidence: 96%

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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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Bacterial Lipopolysaccharide and IFN-γ Induce Toll-Like Receptor 2 and Toll-Like Receptor 4 Expression in Human Endothelial Cells: Role of NF-κB Activation

Cited by 427 publications

References 65 publications

Microglia are required for astroglial toll‐like receptor 4 response and for optimal TLR2 and TLR3 response

Microglia are required for astroglial toll‐like receptor 4 response and for optimal TLR2 and TLR3 response

Receptors involved in cell activation by antiphospholipid antibodies

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

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