TREM-1 expression is increased in the synovium of rheumatoid arthritis patients and induces the expression of pro-inflammatory cytokines

Abstract

These findings suggest that the presence of high levels of functionally active TREM-1 in RA synovium may contribute to the development or maintenance of RA, or both. Inhibiting TREM-1 activity may, therefore, have a therapeutic effect on RA. High levels of soluble TREM-1 in the plasma of RA patients compared with healthy volunteers may indicate disease activity.

Hypoxia modulates the gene expression profile of immunoregulatory receptors in human mature dendritic cells: identification of TREM-1 as a novel hypoxic marker in vitro and in vivo

“…As shown in Figure 7A, plasma sTREM concentrations in JIA patients (61-394 pg/mL) were significantly higher (P Ͻ .01) than those in control subjects (12-16 pg/mL) and were further increased (P Ͻ .001) in matched SF samples (1120-3800 pg/mL). These data are in line with previous observations in other forms of inflammatory arthritis, such as rheumatoid arthritis, 26,27 indicating disease activity.…”

“…by guest www.bloodjournal.org From TREM-1 is expressed in vivo on H-mDCs recruited to the synovial fluid of JIA patients TREM-1 has been recently implicated in the pathogenesis of noninfectious inflammatory disorders, including rheumatoid arthritis. 26,27 Hypoxia is a common feature of the inflamed rheumatoid synovium, 8,28 and evidence suggests that DCs are enriched in arthritic joints playing a role in the initiation and perpetuation of the inflammatory process. 23,29 To evaluate TREM-1 ϩ mDC occurrence in vivo, we investigated whether TREM-1 was expressed in synovial mDCs from children affected by JIA.…”

TNF-α promotes LPA1- and LPA3-mediated recruitment of leukocytes in vivo through CXCR2 ligand chemokines

“…Moreover, a soluble form of TREM-1 was detected in the blood sample of human patients with infl ammatory disorders, such as sepsis ( 52 ), pneumonia ( 53 ), acute pancreatitis ( 54 ), and peptic ulcer disease ( 55 ). Very recently, Kuai et al reported that TREM-1 expression is increased in the synovium of RA patients ( 56 ). The expression of an eosinophil-recruiting chemokine CCL1 (I-309), which has been implicated in infl ammatory diseases, such as atopic dermatitis ( 57 ) and asthma ( 58 ), was also seen to be upregulated by LPA in TNF-␣ -primed air pouches.…”

Triggering receptor expressed on myeloid cells -1 as a new therapeutic target during inflammatory diseases

“…62 In vitro stimulation of human primary synovial cells isolated from RA patients (comprising synoviocytes but also infiltrated leucocytes) by αTREM-1 showed increased cytokine production (TNFα, IL-8, IL-1β, GM-CSF) as compared to controls. These data suggest that TREM-1 could play a role in amplifying inflammation during arthritis and that modulating the TREM-1 beneficial.…”

“…Indeed, infiltrated leucocytes in inflammatory synovia expressed high levels of TREM-1. 62 Moreover, patients with RA or septic arthritis showed elevated levels of sTREM-1 in synovial fluid that correlated with TNFα concentration and with the number of infiltrated leucocytes. TREM-1 expressing cells were of myelomonocytic lineage and synoviocytes didn't express TREM-1.…”