Differential regulation of proinflammatory mediators following LPS- and ATP-induced activation of monocytes from patients with antiphospholipid syndrome.
15 Feb 2015-BioMed Research International (Hindawi Publishing Corporation)-Vol. 2015, pp 292851-292851
TL;DR: Increased sensitivity of APS cells to LPS that may contribute to thrombus formation and enhance development or progression of autoimmune processes is indicated.
Abstract: Antiphospholipid syndrome (APS) is an acquired autoimmune disorder characterized by recurrent thrombosis and pregnancy morbidity in association with the presence of antiphospholipid antibodies. Growing evidence supports the involvement of monocytes in APS pathogenesis. Inflammatory activation of monocytes promotes thrombus formation and other APS complications. However, mechanisms underlying their activation are poorly investigated. We aimed to determine transcriptional activity of monocytes after exposing them to low concentrations of lipopolysaccharide (LPS) and LPS + adenosine triphosphate (ATP) using comparative qRT-PCR. The results showed that LPS significantly increased transcriptional levels of TLR2, IL-23, CCL2, CXCL10, IL-1β, and IL-6 in APS cells, while, in cells from healthy donors, LPS resulted in IL-6 and STAT3 elevated mRNAs. Double stimulation of the cells resulted in decreased mRNA levels of NLRP3 in monocytes isolated from healthy donors and CCL2, IL-1β in APS cells. By contrast, TLR2 mRNAs were elevated in both investigated groups after culture of the cells with LPS + ATP. Thus, the findings indicate increased sensitivity of APS cells to LPS that may contribute to thrombus formation and enhance development or progression of autoimmune processes. Low concentrations of ATP diminish LPS-induced inflammatory state of APS monocytes which might be a potential mechanism which regulates inflammatory state of the cells.
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TL;DR: A plea is made for future extensive immune cell profiling by a systems medicine approach in order to better unravel the pathogenesis of APS to gain more insight in the role of the immune system in APS as well as having the potential to reveal biomarkers or novel therapeutic targets.
53 citations
TL;DR: This review summarizes and critically assess the pathogenic and non-pathogenic formation of aPLs and its contribution to the development of APS.
Abstract: Antiphospholipid antibodies (aPLs) comprise a diverse family of autoantibodies targeted against proteins with the affinity toward negatively charged phospholipids or protein-phospholipid complexes. Their clinical significance, including prothrombotic potential of anti-cardiolipin antibodies (aCLs), anti-β2-glycoprotein I antibodies (aβ2-GPIs), and lupus anti-coagulant (LA), is well-established. However, the ontogeny of these pathogenic aPLs remains less clear. While transient appearance of aPLs could be induced by various environmental factors, in genetically predisposed individuals these factors may eventually lead to the development of the antiphospholipid syndrome (APS). Since the first description of APS, it has been found that a wide variety of microbial and viral agents influence aPLs production and contribute to clinical manifestations of APS. Many theories attempted to explain the pathogenic potential of different environmental factors as well as a phenomenon termed molecular mimicry between β2-GPI molecule and infection-relevant structures. In this review, we summarize and critically assess the pathogenic and non-pathogenic formation of aPLs and its contribution to the development of APS.
38 citations
Cites background from "Differential regulation of proinfla..."
...It is a widely accepted view that pathogenesis of many autoimmune diseases is largely driven by inappropriate or inadequate immune responses toward bacterial agents (50, 51)....
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TL;DR: LDL(−) promotes release of biologically active IL-1β in monocytes and MDM by induction of the two steps involved: priming and NLRP3 inflammasome activation.
37 citations
TL;DR: The results suggest that arterial hypertension and monocyte counts may be independent factors for thrombosis recurrence in APS, and may support the evaluation of therapeutic measures to a rigid control of blood pressures and modulation of inflammatory response in APs, as additional prophylaxis against the recurrence of vascular events.
25 citations
Cites background from "Differential regulation of proinfla..."
...Monocytes have been recognized as key cells for the pathogenesis of APS [11] and previous “in vitro” and clinical studies have demonstrated an increased activation of monocytes in patients with APS [27,28]....
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...For the pathogenesis of thrombotic APS, the immune-complex formed by aCL or aβ2GP1 and their antigens, in particular LDL oxidized, would activatemonocytes to express tissue factor, to secrete inflammatory cytokines [11,27] and possibly contribute to the formation of atherosclerotic plaques on the vascular wall [30]....
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TL;DR: Levels of sTREM-1 might serve as a biomarker for thrombosis in patients with primary antiphospholipid syndrome as well as other predictors (thrombotic PAPS-ever, age, and sex).
Abstract: Soluble triggering receptor expressed on myeloid cells-1 (sTREM-1) is an innate-immune receptor found in blood. Its presence reflects innate immune cell activation. We sought to investigate plasma sTREM-1 levels in patients with primary antiphospholipid syndrome (PAPS). A cross-sectional, case-control design was used. Plasma sTREM-1 levels were analyzed by enzyme-linked immunosorbent assay (ELISA) in consecutive patients diagnosed with PAPS or asymptomatic antiphospholipid antibody (APLA) carriers and controls. The study cohort included 33 patients with PAPS, 10 asymptomatic APLA carriers, and 73 controls. Mean plasma sTREM-1 levels were significantly higher in patients with PAPS (299.2 ± 146.7 pg/ml) and thrombotic PAPS-ever (current and past thrombotic event) (327.2 ± 151.3 pg/ml) compared with controls (230.2 ± 85.5 pg/ml; p = 0.006 and p = 0.003, respectively), patients with thrombotic PAPS compared with patients with past obstetric APS (195.12 ± 58.52 pg/ml, p = 0.01) and APLA carriers (215.8 ± 51.6 pg/ml, p = 0.02), patients with current thrombotic PAPS (429.5 ± 227.5 pg/ml) compared with patients with past thrombotic PAPS (289.5 ± 94.65 pg/ml, p = 0.01), and patients with PAPS who had ever had a stroke or venous thromboembolic event compared with patients who had not (p = 0.007 and p = 0.02, respectively). On receiver operator characteristic curve analysis, plasma sTREM-1 levels differentiated patients with current thrombotic PAPS from asymptomatic APLA carriers and controls, with an area under the curve of 0.7292 (p = 0.0014) and 0.88 (p < 0.0001), respectively. Multivariate regression analysis to identify sTREM-1 predictors (thrombotic PAPS-ever, age, and sex) yielded an independent association of sTREM-1 levels with thrombotic PAPS (p < 0.0001). Plasma sTREM-1 levels are significantly elevated in patients with thrombotic PAPS. Levels of sTREM-1 might serve as a biomarker for thrombosis in patients with PAPS.
10 citations
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"Differential regulation of proinfla..." refers background in this paper
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1,981 citations
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1,393 citations
TL;DR: In humans and mice, monocytes are divided into two major subsets that either specifically traffic into inflamed tissues or, in the absence of overt inflammation, constitutively maintain tissue macrophage/DC populations.
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1,075 citations
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