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

Bostancı, Nagihan; Thurnheer, Thomas; Belibasakis, Georgios N.

doi:10.1016/j.molimm.2011.09.012

Cited by 38 publications

(78 citation statements)

References 70 publications

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“…and in vitro models by agonist monoclonal antibodies further stimulates the production of pro-inflammatory cytokines (Bleharski et al, 2003;Bostanci et al, 2011;Bouchon et al, 2001;Radsak et al, 2004). A synergism exists between the activation of TREM-1 and toll-like receptors or Nod-like receptors, resulting in amplification of pro-inflammatory cytokines, including tumor necrosis factor (TNF)-α, interleukin (IL)-1β, and inhibition of anti-inflammatory cytokines such as IL-10 (Bleharski et al, 2003).…”

Section: The Engagement Of Trem-1 In In Vivomentioning

confidence: 99%

Elevated Oral and Systemic Levels of Soluble Triggering Receptor Expressed on Myeloid Cells-1 (sTREM-1) in Periodontitis

et al. 2012

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The Triggering Receptor Expressed on Myeloid cells 1 (TREM-1) is a cell-surface receptor of the immunoglobulin superfamily, involved in the propagation of the inflammatory response to bacterial challenge. Soluble (s)TREM-1 is released from the cell surface during the course of infection and is a useful inflammatory biomarker in the early diagnosis of systemic sepsis. The hypothesis of this study was that oral and systemic levels of sTREM-1 are elevated in periodontitis. Therefore, the aim was to investigate, by ELISA, the sTREM-1 concentrations in saliva and serum of individuals without periodontitis (control) and persons with chronic or generalized aggressive periodontitis. In saliva, sTREM-1 concentrations were higher in chronic and aggressive periodontitis than in the control group, by 3.3-fold and 5.6-fold, respectively. In serum, these differences were 1.7-fold and 2-fold, respectively. However, there were no significant differences between the two forms of periodontitis, neither in saliva nor in serum. Salivary and serum sTREM-1 levels positively correlated with full-mouth clinical periodontal parameters. In conclusion, the increased oral and systemic levels of sTREM-1 in periodontitis denote a value for this molecule as a biomarker for the disease and may also have implications in the association between periodontal infections and systemic inflammatory response. ABSTRACTThe Triggering Receptor Expressed on Myeloid cells 1 (TREM-1) is a cell surface receptor of the immunoglobulin superfamily, involved in the propagation of the inflammatory response to bacterial challenge. Soluble (s)TREM-1 is released from the cell surface during the course of infection, and is a useful inflammatory biomarker in the early diagnosis of systemic sepsis. The hypothesis of this study is that oral and systemic levels of sTREM-1 are elevated in periodontitis. Therefore, the aim was to investigate by ELISA the sTREM-1 concentrations in saliva and serum of nonperiodontitis subjects (control) and patients with chronic or generalized aggressive periodontitis. In saliva, sTREM-1 concentrations were higher in chronic and aggressive periodontitis than the control group, by 3.3-fold and 5.6-fold, respectively.In serum, these differences were 1.7-fold and 2-fold, respectively. However, there were no significant differences between the two forms of periodontitis, neither in saliva nor in serum. Salivary and serum sTREM-1 levels positively correlated with full mouth clinical periodontal parameters. In conclusion, the increased oral and systemic levels of sTREM-1 in periodontitis denote a value for this molecule as a biomarker for the disease, and may also have implications in the association between periodontal infections and systemic inflammatory response.3

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Section: The Engagement Of Trem-1 In In Vivomentioning

confidence: 99%

Elevated Oral and Systemic Levels of Soluble Triggering Receptor Expressed on Myeloid Cells-1 (sTREM-1) in Periodontitis

et al. 2012

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“…TLR-induced signals (especially TLR-2) are amplified by activated TREM-I leading specifically to an increase in cytokine (IL-1α, TNF-α, Granulocyte-macrophage colony-stimulating factor (GM-CSF)) and chemokine (IL-8, Monocyte chemotactic protein 1 (MCP-1), MCP-3, Macrophage Inflammatory Proteins (MIP-1) production [27]. Blocking TREM-1 decreases Th1 signaling through IL-1β, Interferon (IFN)-γ, and IL-6 and increases Th2 production of IL-4, IL-5, and IL-10 [8, 28, 29]. Toll-like Receptors (TLRs) are germ line encoded receptors of the innate immune response responsible for distinguishing between microorganisms and responding appropriately to specific microbes [30].…”

Section: Triggering Receptor Expressed On Myeloid Cells (Trem)-1mentioning

confidence: 99%

“…Upon recognition of bacterial challenge by TLRs and PAMPs, TREM-1/DAP12 interactions mediate downstream signaling to increase proinflammatory cytokine production [27]. Research conducted by Bostanci et al [8] revealed P. gingivalis can disrupt the TREM-1/DAP12 signaling pathway. Through this mechanism, P. gingivalis was determined to have engagement with TREM-1 and may act to regulate systemic inflammation [8].…”

Section: Triggering Receptor Expressed On Myeloid Cells (Trem)-1mentioning

confidence: 99%

“…Research conducted by Bostanci et al [8] revealed P. gingivalis can disrupt the TREM-1/DAP12 signaling pathway. Through this mechanism, P. gingivalis was determined to have engagement with TREM-1 and may act to regulate systemic inflammation [8]. …”

Section: Triggering Receptor Expressed On Myeloid Cells (Trem)-1mentioning

confidence: 99%

“…Non-surgical periodontal therapy (NSPT) has shown a beneficial effect on inflammation of the vascular wall attributed to periodontitis by lowering plasma interleukin (IL)-6, improving the lipid profile, and improving elasticity of the aortic artery [7]. Though there has not been definitive research establishing the link between periodontal and systemic inflammation, there has been research showing NSPT can reduce bacterial challenges, resolve inflammation, and restore health [4,8,9]. …”

Section: Introductionmentioning

confidence: 99%

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Triggering receptor expressed on myeloid cells in the pathogenesis of periodontitis: potential novel treatment strategies

Rudick

Miyamoto

Lang

et al. 2017

Expert Review of Clinical Immunology

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Introduction Periodontal diseases are polymicrobial inflammatory disorders of the tissue, ligament, and bone structures supporting teeth. Periodontitis (inflammation with corresponding loss of attachment) affects 40–50% of adults. Recently, members of the Triggering Receptor on Myeloid Cell (TREM) family have been studied to determine their relationship to these diseases. Areas covered TREM-1 is a receptor expressed on the surface of PMNs, monocytes, macrophages, dendritic cells, vascular smooth muscle cells, and keratinocytes upregulated in the presence of periodontal inflammation. TREM-1 expression can be upregulated by oral bacterium Porphyromonas gingivalis that can be abrogated by a sub-antimicrobial dose of doxycycline. When cleaved from the cell surface, a soluble form of TREM-1 (sTREM-1) can be used as a biomarker of inflammation and might also provide a link between oral and systemic inflammation. While less understood, TREM-2 has a role in osteoclastogenesis which could contribute to the alveolar bone destruction seen in more advanced periodontitis. Expert Commentary Additional studies to simulate biofilm microenvironment in TREM research are warranted. Longitudinal studies determining TREM-1, sTREM-1, and TREM-2 levels in tissues over time and progression of periodontal diseases would provide valuable information in the role of TREM receptors as indicators of or contributors to the disease process.

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Evaluation of metronidazole‐loaded poly(3‐hydroxybutyrate) membranes to potential application in periodontitis treatment

et al. 2015

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Guided tissue regeneration is a technique used for periodontium reconstruction. This technique uses barrier membranes, which prevent epithelial growth in the wound site and may also be used to release antibiotics, to protect the wound against opportunistic infections. Periodontal poly(3-hydroxybutyrate) membranes containing metronidazole (a drug used to help in infection control) were produced and characterized. The kinetic mechanism of the metronidazole delivery of leached and nonleached membrane as well as its cytotoxicity and structural integrity were evaluated. Poly(3-hydroxybutyrate) membranes containing 0.5-2 wt % of the drug and 20 wt % of the plasticizer were manufactured via compression molding. Based on morphological analysis, membranes loaded with 2% metronidazole were considered for detailed studies. The results revealed that metronidazole delivery by the leached membranes seemed to follow the Fick's law. Membranes were noncytotoxic. The amount of metronidazole delivered was in the range of the minimal inhibitory concentration for Porphyromonas gingivalis, and the membranes inhibited the proliferation of these bacteria. Besides, they maintained their mechanical resistance after 30 days of immersion in phosphate buffer at pH 7.4.

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

Cited by 38 publications

References 70 publications

Elevated Oral and Systemic Levels of Soluble Triggering Receptor Expressed on Myeloid Cells-1 (sTREM-1) in Periodontitis

Elevated Oral and Systemic Levels of Soluble Triggering Receptor Expressed on Myeloid Cells-1 (sTREM-1) in Periodontitis

Triggering receptor expressed on myeloid cells in the pathogenesis of periodontitis: potential novel treatment strategies

Evaluation of metronidazole‐loaded poly(3‐hydroxybutyrate) membranes to potential application in periodontitis treatment

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