Toll-like receptor 1 inhibits Toll-like receptor 4 signaling in endothelial cells

Spitzer, Jessica H.; Visintin, Alberto; Mazzoni, Alessandra; Kennedy, Margaret; Segal, David M.

doi:10.1002/1521-4141(200204)32:4<1182::aid-immu1182>3.0.co;2-9

Cited by 36 publications

(16 citation statements)

References 24 publications

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“…Adding further to the complexity regarding the interaction of TLRs with their respective ligands is the observation that specific TLRs may interact with co-receptors of other TLRs. Spitzer et al [76] have demonstrated that TLR1 interacts and modulates the signaling of TLR4 and also that CD14 is required for both TLR4-and TLR2-dependent signaling. Finally, CD14 also interacts with endosomal TLR8 [77][78][79].…”

Section: Internalization and Apla Receptorsmentioning

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: Internalization and Apla Receptorsmentioning

confidence: 99%

Receptors involved in cell activation by antiphospholipid antibodies

Brandt

Kruithof

Moerloose

2013

Thrombosis Research

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“…One report showed TLR1 immunoreactivity in atherosclerotic endothelium (21), while another failed to demonstrate TLR1 expression by human microvascular EC lines in vitro, even though TLR1 transfection inhibited TLR4-dependent signaling (22).…”

Section: Innate Immunitymentioning

confidence: 99%

Immune Regulation by Microvascular Endothelial Cells: Directing Innate and Adaptive Immunity, Coagulation, and Inflammation

Danese¹,

Dejana

Fiocchi

2007

The Journal of Immunology

252

203

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An effective immune response depends not only on the proper activation, regulation, and function of immune cells, but also on their distribution and retention in diverse tissue microenvironments where they encounter a number of stimuli and other cell types. These activities are mediated by endothelial cells, which form specialized microcirculatory networks used by immune cells under both physiological and pathological circumstances. Endothelial cells represent a highly heterogeneous population of cells with the ability to interact with and modulate the function of immune cells. This review is focused on the role of microvascular endothelial cells in innate and adaptive immunity, inflammation, coagulation, angiogenesis, and the therapeutic implications of targeting endothelial cells in selected autoimmune and chronic inflammatory disorders.

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“…Recent studies have demonstrated that both TLR2 and TLR1 signaling are required to generate an immune response to the Borrelia burgdorferi PAMP OspA (56). However, in certain overexpression systems expression of TLR1 inhibited TLR2 or TLR4 signaling (52,57). Toll inhibitory protein (Tollip), a molecule that interferes with IL-1R-activated kinase (IRAK) signaling, inhibits TLR2 and TLR4 responsiveness and may serve to limit proinflammatory cytokine secretion (58 -60).…”

Section: Human Intestinal Epithelial Cells Are Broadly Unresponsive Tmentioning

confidence: 99%

Human Intestinal Epithelial Cells Are Broadly Unresponsive to Toll-Like Receptor 2-Dependent Bacterial Ligands: Implications for Host-Microbial Interactions in the Gut

Melmed¹,

Thomas²,

Lee³

et al. 2003

The Journal of Immunology

393

281

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Intestinal epithelial cells (IEC) interact with a high density of Gram-positive bacteria and are active participants in mucosal immune responses. Recognition of Gram-positive organisms by Toll-like receptor (TLR)2 induces proinflammatory gene expression by diverse cells. We hypothesized that IEC are unresponsive to Gram-positive pathogen-associated molecular patterns and sought to characterize the functional responses of IEC to TLR2-specific ligands. Human colonic epithelial cells isolated by laser capture microscopy and IEC lines (Caco-2, T84, HT-29) were analyzed for expression of TLR2, TLR6, TLR1, and Toll inhibitory protein (Tollip) mRNA by RT-PCR and quantitative real-time PCR. Response to Gram-positive bacterial ligands was measured by NF-κB reporter gene activation and IL-8 secretion. TLR2 protein expression was analyzed by immunofluorescence and flow cytometry. Colonic epithelial cells and lamina propria cells from both uninflamed and inflamed tissue demonstrate low expression of TLR2 mRNA compared with THP-1 monocytes. IECs were unresponsive to TLR2 ligands including the staphylococcal-derived Ags phenol soluble modulin, peptidoglycan, and lipotechoic acid and the mycobacterial-derived Ag soluble tuberculosis factor. Transgenic expression of TLR2 and TLR6 restored responsiveness to phenol soluble modulin and peptidoglycan in IEC. In addition to low levels of TLR2 protein expression, IEC also express high levels of the inhibitory molecule Tollip. We conclude that IEC are broadly unresponsive to TLR2 ligands secondary to deficient expression of TLR2 and TLR6. The relative absence of TLR2 protein expression by IEC and high level of Tollip expression may be important in preventing chronic proinflammatory cytokine secretion in response to commensal Gram-positive bacteria in the gut.

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Toll-like receptor 1 inhibits Toll-like receptor 4 signaling in endothelial cells

Cited by 36 publications

References 24 publications

Receptors involved in cell activation by antiphospholipid antibodies

Receptors involved in cell activation by antiphospholipid antibodies

Immune Regulation by Microvascular Endothelial Cells: Directing Innate and Adaptive Immunity, Coagulation, and Inflammation

Human Intestinal Epithelial Cells Are Broadly Unresponsive to Toll-Like Receptor 2-Dependent Bacterial Ligands: Implications for Host-Microbial Interactions in the Gut

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