Endotoxemia in Human Septic Shock

Danner, Robert L.; Elin, Ronald J.; Hosseini, Jeanette M.; Wesley, Robert; Reilly, Joseph; Parillo, Joseph E.

doi:10.1378/chest.99.1.169

Cited by 600 publications

(137 citation statements)

References 33 publications

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“…LTA, a key cell wall component of Gram-positive bacteria, seems to function as an immune activator with characteristics very similar to LPS. Although these two bacterial components seem to induce the same end result (49), there seem to be significant difference between sepsis caused by Gram-positive and Gram-negative bacteria, mainly in the host responses against them (50). In this work we have chosen to investigate whether LTA binding and internalization are similar to those that have recently been reported for bacterial LPS (27).…”

Section: Discussionmentioning

confidence: 94%

Lipoteichoic Acid and Toll-like Receptor 2 Internalization and Targeting to the Golgi Are Lipid Raft-dependent

Triantafilou

Manukyan

Mackie

et al. 2004

Journal of Biological Chemistry

118

113

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Lipoteichoic acid (LTA), a key cell wall component of Gram-positive bacteria, seems to function as an immune activator with characteristics very similar to lipopolysaccharide from Gram-negative bacteria. It has been shown that LTA binds CD14 and triggers activation via Toll-like receptor 2, but whether the activation occurs at the cell surface or internalization is required to trigger signaling has yet to be demonstrated. In this work we have investigated LTA binding and internalization and found that LTA and its receptor molecules accumulate in lipid rafts and are subsequently targeted rapidly to the Golgi apparatus. This internalization seems to be lipid raft-dependent because raft-disrupting drugs inhibited LTA/Toll-like receptor 2 colocalization in the Golgi. Similarly to lipopolysaccharide, LTA activation occurs at the cell surface, and the observed trafficking is independent of signaling.

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Section: Discussionmentioning

confidence: 94%

Lipoteichoic Acid and Toll-like Receptor 2 Internalization and Targeting to the Golgi Are Lipid Raft-dependent

Triantafilou

Manukyan

Mackie

et al. 2004

Journal of Biological Chemistry

118

113

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“…Although the LPS-induced inflammatory response is indispensable for controlling the growth of pathogenic microorganisms (5), excessive cytokine production can be harmful to the host and may even contribute to a life-threatening condition termed septic shock (6). In addition, TLR4-initiated signaling pathways have recently been implicated in the pathogenesis of various autoimmune and chronic inflammatory diseases.…”

mentioning

confidence: 99%

LIND/ABIN-3 Is a Novel Lipopolysaccharide-inducible Inhibitor of NF-κB Activation

Wullaert

Verstrepen

Huffel

et al. 2007

Journal of Biological Chemistry

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Recognition of lipopolysaccharide (LPS) by Toll-like receptor (TLR)4 initiates an intracellular signaling pathway leading to the activation of nuclear factor-B (NF-B). Although LPS-induced activation of NF-B isThe innate immune response to microbial pathogens begins when pathogen-associated molecular patterns meet their cognate Toll-like receptors (TLRs) 8 on effector cells of the immune system, such as monocytes and macrophages (1). Lipopolysaccharide (LPS), an integral cell wall component of Gram-negative bacteria and one of the most potent stimulators in innate immunity, is recognized by the TLR4-MD2 receptor complex (2). In the past years, much progress has been made in understanding the intracellular signaling cascades that are initiated when LPS stimulates TLR4 (reviewed in Refs. 3 and 4). Ligation of the TLR4-MD2 complex by LPS initially results in the recruitment of myeloid differentiation factor (MyD)88 and MyD88-adaptor like (Mal), also called TIRAP, to the receptor cytoplasmic domain. MyD88 then facilitates recruitment of the serine/threonine kinases IL-1R-associated kinase (IRAK)-1 and -4, thus enabling IRAK4 to phosphorylate IRAK1. The latter subsequently dissociates from the receptor complex and associates with tumor necrosis factor (TNF) receptor-associated factor (TRAF)6, constituting a cytoplasmic signaling complex. Upon ubiquitination, TRAF6 activates transforming growth factor-␤-activated kinase 1, which in turn activates the inhibitor of B kinase (IKK) complex that consists of the regulatory subunit IKK␥ (also known as NEMO) and the kinases IKK␣ and IKK␤. The latter eventually phosphorylates the inhibitory IB proteins, resulting in their ubiquitination and degradation. This allows the transcription factor NF-B to translocate to the nucleus and initiate transcription of inflammatory cytokines, such as TNF, which contribute to mounting an inflammatory response. Apart from this MyD88-dependent signaling pathway, TLR4 also initiates a MyD88-independent signaling pathway that is mediated by the adaptor proteins Toll/IL-1 receptor domain domain-containing adaptor-inducing interferon-␤ (TRIF; also known as TICAM-1) and TRIFrelated adaptor molecule (also known as TICAM-2). Although

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“…Production of inflammatory mediators and pro-inflammatory cytokines by innate immune cells is indispensable for the efficient control of growth and dissemination of invading pathogens. However, excessive and uncontrolled production of inflammatory mediators and pro-inflammatory cytokines caused by bacterial infection is potentially harmful to the host and may lead to severe systematic inflammatory complications, including microcirculatory dysfunction, tissue damage, septic shock, and death (2)(3)(4)(5). Vertebrate and bacterial DNA have marked differences in the frequency of CpG dinucleotides and their cytosine methylation (only vertebrate DNA shows extensive under-representation and methylation of CpG dinucleotides, termed CpG suppression) (6).…”

mentioning

confidence: 99%

CpG DNA-mediated Induction of Acute Liver Injury in d-Galactosamine-sensitized Mice

Yoon

Park

et al. 2006

Journal of Biological Chemistry

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Endotoxemia in Human Septic Shock

Cited by 600 publications

References 33 publications

Lipoteichoic Acid and Toll-like Receptor 2 Internalization and Targeting to the Golgi Are Lipid Raft-dependent

Lipoteichoic Acid and Toll-like Receptor 2 Internalization and Targeting to the Golgi Are Lipid Raft-dependent

LIND/ABIN-3 Is a Novel Lipopolysaccharide-inducible Inhibitor of NF-κB Activation

CpG DNA-mediated Induction of Acute Liver Injury in d-Galactosamine-sensitized Mice

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