CD14 directly binds to triacylated lipopeptides and facilitates recognition of the lipopeptides by the receptor complex of Toll-like receptors 2 and 1 without binding to the complex

Nakata, Takashi; Yasuda, Motoaki; Fujita, Mari; Kataoka, Hideo; Kiura, Kazuto; Sano, Hidehiko; Shibata, Kenichiro

doi:10.1111/j.1462-5822.2006.00756.x

Cited by 123 publications

(132 citation statements)

References 29 publications

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“…Notably, it has been established that OxPAPC binds to serum accessory proteins such as LBP and CD14 and competitively inhibits the binding of LPS to these proteins (17). Likewise, it has been shown that both di-acyl and tri-acyl bacterial lipopeptides bind to CD14 and LBP (35,47) and that CD14 and LBP are required for enhanced cellular sensitivity to bacterial lipopeptides (32,34). Thus, it is likely that the established binding of OxPAPC to CD14 and LBP (17) also contributes to the inhibition of cellular responsiveness to lipopeptides via TLR2.…”

Section: Discussionmentioning

confidence: 99%

“…7A). Because OxPAPC has been shown to bind to CD14 (17) and sCD14 has been shown to play a role in lipopeptide signaling (32,34,35), we examined whether supplementation of the culture medium with recombinant sCD14 alone may also reverse OxPAPC-induced inhibition of TLR2 signaling. Consistent with a role for this protein, OxPAPC inhibition of Pam 3 CSK 4 signaling was reversed by sCD14 supplementation in a dose-dependent fashion (Fig.…”

Section: Oxpapc Inhibits Signaling Via Tlr2 and Tlr4 But Not Othermentioning

confidence: 99%

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Oxidized Phospholipid Inhibition of Toll-like Receptor (TLR) Signaling Is Restricted to TLR2 and TLR4

Erridge

Kennedy

Spickett

et al. 2008

Journal of Biological Chemistry

213

124

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Section: Discussionmentioning

confidence: 99%

Section: Oxpapc Inhibits Signaling Via Tlr2 and Tlr4 But Not Othermentioning

confidence: 99%

Oxidized Phospholipid Inhibition of Toll-like Receptor (TLR) Signaling Is Restricted to TLR2 and TLR4

Erridge

Kennedy

Spickett

et al. 2008

Journal of Biological Chemistry

213

124

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“…CD14 and vitronectin facilitate the transfer of lipopeptides to the TLR2 receptor complex (19,20). It therefore appears that multiple accessory proteins are required by both TLR2 and TLR4 for optimum responses to lipid-based agonists.…”

Section: Discussionmentioning

confidence: 99%

TRIL, a Functional Component of the TLR4 Signaling Complex, Highly Expressed in Brain

Carpenter

Carlson²,

Dellacasagrande

et al. 2009

The Journal of Immunology

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TLR4 is the primary sensor of LPS. In this study, we describe for the first time TLR4 interactor with leucine-rich repeats (TRIL), which is a novel component of the TLR4 complex. TRIL is expressed in a number of tissues, most prominently in the brain but also in the spinal cord, lung, kidney, and ovary. TRIL is composed of a signal sequence, 13 leucine-rich repeats, a fibronectin domain, and a single transmembrane spanning region. TRIL is induced by LPS in the human astrocytoma cell line U373, in murine brain following i.p. injection, and in human PBMC. Endogenous TRIL interacts with TLR4 and this interaction is greatly enhanced following LPS stimulation. TRIL also interacts with the TLR4 ligand LPS. Furthermore, U373 cells stably overexpressing TRIL display enhanced cytokine production in response to LPS. Finally, knockdown of TRIL using small interfering RNA attenuates LPS signaling and cytokine production in cell lines, human PBMC, and primary murine mixed glial cells. These results demonstrate that TRIL is a novel component of the TLR4 complex which may have particular relevance for the functional role of TLR4 in the brain.

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“…1 ligands of >TLRs require presentation via a coreceptor. The coreceptor CD14 has been implicated in facilitating TLR-mediated responses to bacterial lipopeptides by enhancing the physical proximity of the ligand to the TLR heterodimers, without binding directly to the receptor complex (30)(31)(32). However, as demonstrated above, soluble CD14 did not inhibit cell migration in our system (Supplemental Fig.…”

Section: Cd16mentioning

confidence: 61%

Cells Exposed to Sublethal Oxidative Stress Selectively Attract Monocytes/Macrophages via Scavenger Receptors and MyD88-Mediated Signaling

Geiger-Maor

Levi

Even-Ram

et al. 2012

The Journal of Immunology

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The innate immune system responds to endogenous molecules released during cellular stress or those that have undergone modifications normally absent in healthy tissue. These structures are detected by pattern-recognition receptors, alerting the immune system to “danger.” In this study, we looked for early signals that direct immune cells to cells undergoing stress before irreversible damage takes place. To avoid detecting signals emanating from apoptotic or necrotic cells we exposed fibroblasts to sublethal oxidative stress. Our results indicate that both nonenzymatic chemical reactions and aldehyde dehydrogenase-2–mediated enzymatic activity released signals from fibroblasts that selectively attracted CD14+ monocytes but not T, NK, and NKT cells or granulocytes. Splenocytes from MyD88−/− mice did not migrate, and treatment with an inhibitory peptide that blocks MyD88 dimerization abrogated human monocyte migration. Monocyte migration was accompanied by downmodulation of CD14 expression and by the phosphorylation of IL-1R–associated kinase 1, a well-known MyD88-dependent signaling molecule. The scavenger receptor inhibitors, dextran sulfate and fucoidan, attenuated monocyte migration toward stressed cells and IL-1R–associated kinase 1 phosphorylation. Surprisingly, although monocyte migration was MyD88 dependent, it was not accompanied by inflammatory cytokine secretion. Taken together, these results establish a novel link between scavenger receptors and MyD88 that together function as sensors of oxidation-associated molecular patterns and induce monocyte motility. Furthermore, the data indicate that MyD88 independently regulates monocyte activation and motility.

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CD14 directly binds to triacylated lipopeptides and facilitates recognition of the lipopeptides by the receptor complex of Toll-like receptors 2 and 1 without binding to the complex

Cited by 123 publications

References 29 publications

Oxidized Phospholipid Inhibition of Toll-like Receptor (TLR) Signaling Is Restricted to TLR2 and TLR4

Oxidized Phospholipid Inhibition of Toll-like Receptor (TLR) Signaling Is Restricted to TLR2 and TLR4

TRIL, a Functional Component of the TLR4 Signaling Complex, Highly Expressed in Brain

Cells Exposed to Sublethal Oxidative Stress Selectively Attract Monocytes/Macrophages via Scavenger Receptors and MyD88-Mediated Signaling

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