TREM‐1 expression in macrophages is regulated at transcriptional level by NF‐κB and PU.1

Zeng, Heng; Ornatowska, Magdalena; Joo, Myung; Sadikot, Ruxana T.

doi:10.1002/eji.200737270

Cited by 84 publications

(92 citation statements)

References 46 publications

(54 reference statements)

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“…This validation is particularly important in light of a recent gene expression profiling comparison between human and mouse monocyte subsets, which revealed that among the most striking differential expressions was that of TREM-1 (Ingresoll et al, 2010). In agreement with the findings above, up-regulation of TREM-1 gene expression has also been shown in RAW 264.7 cells challenged with either Escherichia coli LPS, or Pseudomonas aeroginosa, and this effect was sustainable over 48 h (Zeng et al, 2007). Nevertheless, in another study it was demonstrated that E. coli LPS does not affect TREM-1 transcription in peripheral blood monocytes, but causes an increase in cell surface TREM-1 expression, denoting an effect on post-transcriptional modulation (Wong-Baeza et al, 2006).…”

Section: Discussionsupporting

confidence: 91%

“…Individual microbial components, such as lipopolysaccharide (LPS) and peptidoglycan, can cause up-regulation of cell surface-localized TREM-1 by monocytes, as well as release in its soluble (s)TREM-1 form (Begum et al, 2004;Gibot et al, 2004b;Gomez-Pina et al, 2007;Murakami et al, 2007;Ramanathan et al, 2005;Zeng et al, 2007). The sTREM-1 appears to be released during the course of infection, and may well be a particularly useful marker of systemic inflammation, as demonstrated in systemic sepsis, septic arthritis, pneumonia (Collins et al, 2009;Gibot et al, 2005;Gibot et al, 2004a;Gibot et al, 2004c;Knapp et al, 2004).…”

Section: Introductionmentioning

confidence: 99%

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Involvement of the TREM-1/DAP12 pathway in the innate immune responses to Porphyromonas gingivalis

Bostancı

Thurnheer

Belibasakis

2011

Molecular Immunology

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Porphyromonas gingivalis, is a Gram-negative obligate oral anaerobic bacterium highly implicated in periodontal disease, the most prevalent chronic inflammatory disease, but recent evidence also indicates a potential contribution to systemic inflammation. The Triggering Receptor Expressed on Myeloid cells 1 (TREM-1) is a cell surface receptor of the immunoglobulin superfamily, which, along with its adaptor signalling molecule DAP12, is involved in immune response to bacterial and fungal infections, particularly by amplifying the production of pro-inflammatory cytokines by the host. The aim of the present study was to investigate the effect of P. gingivalis on the expression of the TREM-1/DAP12 pathway, as well as its engagement in pro-inflammatory cytokine production, by the myelomonocytic cell line MonoMac-6. P. gingivalis enhanced TREM-1 gene expression by the cells, concomitantly to an increase of soluble TREM-1 secretion. Engagement of TREM-1, by introducing anti-TREM-1 to the experimental system, resulted in further potentiation of the pro-inflammatory responses to P. gingivalis, as evaluated by a further enhancement of interleukin (IL)-1 and IL-6 secretion. On the contrary, the synthetic TREM-1 antagonist LP17 reduced the P. gingivalis-induced IL-1 and IL-6 secretion by approximately 50%. In conclusion, the putative periodontal pathogen P. gingivalis can positively regulate the expression of the TREM-1/DAP12 pathway in monocytic cells. Moreover, engagement of TREM-1 can further potentiate the pro-inflammatory responses to P. gingivalis infection. This effect may contribute not only to the pathogenesis of inflammatory periodontal disease, but also to the enhancement of systemic inflammation.

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Section: Discussionsupporting

confidence: 91%

Section: Introductionmentioning

confidence: 99%

Involvement of the TREM-1/DAP12 pathway in the innate immune responses to Porphyromonas gingivalis

Bostancı

Thurnheer

Belibasakis

2011

Molecular Immunology

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“…Their study suggests that activation of TREM-1 in response to LPS is related to production of PGE2 in macrophages [23]. In a recent study, we have shown that the TREM-1 gene is regulated at a transcriptional level by NF-kB, PU.1 and AP1 in macrophages in response to LPS [26]. This study for the first time shows that expression of TREM-1 in response to LPS and LTA requires the presence of TLR and indicates that the expression of TREM-1 in response to LTA and LPS occurs as a result of activation of TLR.…”

Section: Discussionmentioning

confidence: 89%

“…For example, NF-kB is activated by the TLR signaling pathway. We have shown that activation of TREM-1 is dependent on NF-kB activation [26]. In addition TREM-1-mediated tyrosine phosphorylation, activation of MAPK, and mobilization of Ca 21 might also lead to the activation of transcription complexes, which could have a synergistic effect with NF-kB in promoting the expression of pro-inflammatory genes.…”

mentioning

confidence: 92%

MYD88‐dependent and ‐independent activation of TREM‐1 via specific TLR ligands

et al. 2009

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Triggering receptor expressed on myeloid cells (TREM)-1 plays an important role in myeloid cell-activated inflammatory responses. Although TLR ligands such as LPS and lipoteichoic acid have been shown to upregulate TREM-1 expression in macrophage and neutrophils, the role of specific TLR in inducing the expression of TREM-1 remains unclear. In this study, we investigated whether the presence of TLR is necessary for the expression of TREM-1. We show that BM-derived macrophages from TLR4 and TLR2 KO mice failed to induce expression of TREM-1 message and protein in response to their specific ligands. Interestingly, the expression of TREM-1 in response to LPS is not altered in myeloid differentiation factor 88 (MyD88) KO macrophages, suggesting that downstream of TLR a MyD88-independent pathway induces the expression of TREM-1. Inhibiting toll/IL-1R domain-containing adaptor-inducing IFN-b (TRIF) expression by siRNA decreased TREM-1 expression in response to LPS, suggesting that the expression of TREM-1 in response to LPS was mediated by the TRIF signaling pathway. On the other hand, the expression of TREM-1 in response to lipoteichoic acid is dependent on MyD88 expression. These data indicate that the expression of TREM-1 in response to TLR ligands occurs secondary to downstream signaling events and that the presence of TLR is necessary for the expression of TREM-1 in response to their specific ligands. However, the downstream signaling required for the expression of TREM-1 is dependent on the stimulus and the surface receptor through which the signaling is initiated.Key words: Innate immunity . TLR . TREM-1 IntroductionTriggering receptor expressed on myeloid cells 1 (TREM-1) belongs to the TREM super-family of receptors, which is expressed on monocytes and neutrophils [1][2][3][4][5]. These receptors activate downstream signaling pathways with the help of an adaptor molecule, DAP12 [2]. Although the natural ligands for TREM-1 have not been identified the engagement of TREM-1 synergizes with the effects of the TLR ligands and amplifies the synthesis of inflammatory cytokines [2][3][4]6]. Because blocking of TREM-1 improves the survival of mice with bacterial sepsis TREM-1 has been perceived to play an essential role in acute inflammatory responses in murine models of septic shock [2,[7][8][9][10][11][12][13].In the presence of infection, inflammation is triggered through the recognition of microorganism-by the pathogen associated molecules such as the TLR, which are expressed on the surface of innate immune cells such as monocytes, macrophages, and dendritic cells [14][15][16]. To date ten members of TLR have been identified in human, and 13 in mice, and a series of genetic series have revealed their respective ligands. On engagement with 162ligands, TLR recruit specific adapter molecules that propagate downstream signaling [17]. This interaction then leads to the activation of NF-kB and to the release of pro-inflammatory TNF-a, IL-12, IL-1, IL-6, IL-8, and anti-inflammatory (IL-10 and TGF-b) cytokines [18]. TLR ...

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“…We have shown that the functional consequences of TREM-1 silencing in macrophages include an altered availability of key signaling (CD14, IB␣, and MyD88), and effector molecules (MCP-1, IL-1␤, and IL-6) downstream of TLR activation. Furthermore, the presence of TLRs is necessary for the expression of TREM-1 in response to specific TLR ligands (15)(16)(17). These receptors have thus emerged as potent amplifiers of TLR-initiated inflammatory responses (14,16,18).…”

mentioning

confidence: 99%

Triggering Receptor Expressed on Myeloid Cells 1 (TREM-1)-mediated Bcl-2 Induction Prolongs Macrophage Survival

Yuan

Syed

Panchal

et al. 2014

Journal of Biological Chemistry

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TREM‐1 expression in macrophages is regulated at transcriptional level by NF‐κB and PU.1

Cited by 84 publications

References 46 publications

Involvement of the TREM-1/DAP12 pathway in the innate immune responses to Porphyromonas gingivalis

Involvement of the TREM-1/DAP12 pathway in the innate immune responses to Porphyromonas gingivalis

MYD88‐dependent and ‐independent activation of TREM‐1 via specific TLR ligands

Triggering Receptor Expressed on Myeloid Cells 1 (TREM-1)-mediated Bcl-2 Induction Prolongs Macrophage Survival

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