Lipopolysaccharide Recognition, Cd14, and Lipopolysaccharide Receptors

Ingalls, Robin R.; Heine, Holger; Lien, Egil; Yoshimura, Atsutoshi; Golenbock, Douglas T.

doi:10.1016/s0891-5520(05)70078-7

Cited by 135 publications

(97 citation statements)

References 96 publications

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“…CD14, a glycosylphosphatidylinositol-linked membrane protein that is widely expressed in mononuclear cells, is considered a high affinity receptor for LPS (8,9). However, CD14 lacks a cytoplasmic domain, and there has been a puzzling question as to how CD14 transmits extracellular signals into downstream cytoplasmic signaling pathways.…”

mentioning

confidence: 99%

Murine TOLL-like Receptor 4 Confers Lipopolysaccharide Responsiveness as Determined by Activation of NFκB and Expression of the Inducible Cyclooxygenase

Rhee

Hwang

2000

Journal of Biological Chemistry

231

208

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Genetic evidence indicating that TOLL-like receptor 4 (Tlr4) is the lipopolysaccharide (LPS) receptor in mice was reported. However, biochemical evidence that murine Tlr4 confers LPS responsiveness has not been convincingly demonstrated. Inducible cyclooxygenase (COX-2) is selectively expressed in LPS-stimulated macrophages in part mediated through the activation of NFB. Thus, we determined whether murine Tlr4 confers LPS responsiveness as evaluated by the activation of NFB and COX-2 expression. Transfection of a murine macrophage-like cell line (RAW264.7) with the constitutively active form (⌬Tlr4) of Tlr4 is sufficient to activate NFB and COX-2 expression. However, the truncated form (⌬Tlr4(P712H)) of the missense mutant Tlr4(P712H) found in LPS-hyporesponsive mouse strain (C3H/HeJ) inhibits LPS-induced NFB activation and COX-2 expression. The inability of ⌬Tlr4(P712H) to activate NFB and induce COX-2 expression is rescued by a constitutively active adapter protein myeloid differentiation factor 88 (MyD88), which interacts directly with the cytoplasmic domain of Tlr proteins. Furthermore, MyD88 is co-immunoprecipitated with the wild-type ⌬Tlr4 but not with the ⌬Tlr4(P712H) mutant. Together, these results indicate that Tlr4 confers LPS responsiveness in RAW264.7 cells and suggest that hyporesponsiveness of C3H/HeJ mice to LPS is attributed to the disruption of Tlr4-mediated signaling pathways that results from the inability of the mutant Tlr4(P712H) to interact with MyD88.

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mentioning

confidence: 99%

Murine TOLL-like Receptor 4 Confers Lipopolysaccharide Responsiveness as Determined by Activation of NFκB and Expression of the Inducible Cyclooxygenase

Rhee

Hwang

2000

Journal of Biological Chemistry

231

208

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“…It is established that LPS, TNF-␣, or IFN-␥ act on macrophages through different receptors and signaling pathways (30,31,34). LPS activates macrophage by interacting with CD14 and transduces signals through Toll-like proteins (34,35).…”

Section: Discussionmentioning

confidence: 99%

“…LPS activates macrophage by interacting with CD14 and transduces signals through Toll-like proteins (34,35). TNF-␣ or IFN-␥ bind to their individual receptors and stimulate JAK/STAT activities or TNF receptor-associated proteins (36,37).…”

Section: Discussionmentioning

confidence: 99%

Regulation of the RON Receptor Tyrosine Kinase Expression in Macrophages: Blocking the RON Gene Transcription by Endotoxin-Induced Nitric Oxide

Wang

Fung

Chen

2000

The Journal of Immunology

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Previous studies have shown that activation of the RON receptor tyrosine kinase inhibits inducible NO production in murine peritoneal macrophages. The purpose of this study is to determine whether inflammatory mediators such as LPS, IFN-γ, and TNF-α regulate RON expression. Western blot analysis showed that RON expression is reduced in peritoneal macrophages collected from mice injected with a low dose of LPS. The inhibition was seen as early as 8 h after LPS challenge. Experiments in vitro also demonstrated that the levels of the RON mRNA and protein are diminished in cultured peritoneal macrophages following LPS stimulation. TNF-α plus IFN-γ abrogated macrophage RON expression, although individual cytokines had no significant effect. Because LPS and TNF-α plus IFN-γ induce NO production, we reasoned that NO might be involved in the RON inhibition. Two NO donors, S-nitroglutathione (GSNO) and (±)-S-nitroso-N-acetylpenicillamine (SNAP), directly inhibited macrophage RON expression when added to the cell cultures. Blocking NO production by NO inhibitors like TGF-β prevented the LPS-mediated inhibitory effect. In Raw264.7 cells transiently transfected with a report vector, GSNO or SNAP inhibited the luciferase activities driven by the RON gene promoter. Moreover, GSNO or SNAP inhibited the macrophage-stimulating protein-induced RON phosphorylation and macrophage migration. We concluded from these data that RON expression in macrophages is regulated during inflammation. LPS and TNF-α plus IFN-γ are capable of down-regulating RON expression through induction of NO production. The inhibitory effect of NO is mediated by suppression of the RON gene promoter activities.

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“…(Wright et al, 1990;Espevik et al, 1993;Haziot et al, 1996;Weidemann et al, 1997;Dziarski et al, 1998;Ingalls et al, 1999). CD14 also involves in TLR2-dependent initiation of immune response (Schroder et al, 2003), however, depending on the nature of the ligand, the presence of which is not absolutely required by all TLR2 complexes for signaling activity (Jiang et al, 2005).…”

Section: Tlr2mentioning

confidence: 99%

Herpesviral infection and Toll-like receptor 2

Cai

Zheng

2012

Protein Cell

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In the last decade, substantial progress has been made in understanding the molecular mechanisms involved in the initial host responses to viral infections. Herpesviral infections can provoke an inflammatory cytokine response, however, the innate pathogen-sensing mechanisms that transduce the signal for this response are poorly understood. In recent years, it has become increasingly evident that the Toll-like receptors (TLRs), which are germline-encoded pattern recognition receptors (PRRs), function as potent sensors for infection. TLRs can induce the activation of the innate immunity by recruiting specific intracellular adaptor proteins to initiate signaling pathways, which then culminating in activation of the nuclear factor kappa B (NF-κB) and interferon-regulatory factors (IRFs) that control the transcription of genes encoding type I interferon (IFN I) and other inflammatory cytokines. Furthermore, activation of innate immunity is critical for mounting adaptive immune responses. In parallel, common mechanisms used by viruses to counteract TLR-mediated responses or to actively subvert these pathways that block recognition and signaling through TLRs for their own benefit are emerging. Recent findings have demonstrated that TLR2 plays a crucial role in initiating the inflammatory process, and surprisingly that the response TLR2 triggers might be overzealous in its attempt to counter the attack by the virus. In this review, we summarize and discuss the recent advances about the specific role of TLR2 in triggering inflammatory responses in herpesvirus infection and the consequences of the alarms raised in the host that they are assigned to protect.

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Lipopolysaccharide Recognition, Cd14, and Lipopolysaccharide Receptors

Cited by 135 publications

References 96 publications

Murine TOLL-like Receptor 4 Confers Lipopolysaccharide Responsiveness as Determined by Activation of NFκB and Expression of the Inducible Cyclooxygenase

Murine TOLL-like Receptor 4 Confers Lipopolysaccharide Responsiveness as Determined by Activation of NFκB and Expression of the Inducible Cyclooxygenase

Regulation of the RON Receptor Tyrosine Kinase Expression in Macrophages: Blocking the RON Gene Transcription by Endotoxin-Induced Nitric Oxide

Herpesviral infection and Toll-like receptor 2

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