Differential regulation of proinflammatory mediators following LPS- and ATP-induced activation of monocytes from patients with antiphospholipid syndrome.
Anush Martirosyan,Martin Petrek,Zdenka Navratilova,Armen Blbulyan,Anna Boyajyan,Gayane Manukyan,Gayane Manukyan +6 more
TLDR
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.read more
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Delineating the deranged immune system in the antiphospholipid syndrome
Lucas L van den Hoogen,Joel A G van Roon,Timothy R D J Radstake,Ruth D E Fritsch-Stork,Ronald H. W. M. Derksen +4 more
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.
Journal ArticleDOI
Environmental Triggers of Autoreactive Responses: Induction of Antiphospholipid Antibody Formation.
TL;DR: This review summarizes and critically assess the pathogenic and non-pathogenic formation of aPLs and its contribution to the development of APS.
Journal ArticleDOI
Electronegative LDL induces priming and inflammasome activation leading to IL-1β release in human monocytes and macrophages
Montserrat Estruch,Kristiina Rajamäki,José Luis Sánchez-Quesada,Petri T. Kovanen,Katariina Öörni,Sonia Benitez,Jordi Ordóñez-Llanos +6 more
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.
Journal ArticleDOI
Recurrent thrombosis in antiphospholipid syndrome may be associated with cardiovascular risk factors and inflammatory response.
Sabrina da Silva Saraiva,Isadora Custódio,Bruna M Mazetto,Marina Pereira Collela,Erich Vinicius De Paula,Simone Appenzeller,Joyce Annichino-Bizzachi,Fernanda Andrade Orsi +7 more
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.
Journal ArticleDOI
Elevated plasma level of soluble triggering receptor expressed on myeloid cells-1 is associated with inflammation activity and is a potential biomarker of thrombosis in primary antiphospholipid syndrome
Yonatan Edel,Yonatan Edel,Vitaly Kliminski,Vitaly Kliminski,Elisheva Pokroy-Shapira,Elisheva Pokroy-Shapira,Shirly Oren,Ariela Dortort Lazar,Ariela Dortort Lazar,Yael Pri-Paz Basson,Mohammad Egbaria,Yair Molad,Yair Molad +12 more
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).
References
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14th International Congress on Antiphospholipid Antibodies Task Force report on obstetric antiphospholipid syndrome.
Guilherme Ramires de Jesus,Nancy Agmon-Levin,Carlos Augusto Ferreira de Andrade,Laura Andreoli,Cecilia Beatrice Chighizola,T. Flint Porter,Jane E. Salmon,Robert M. Silver,Angela Tincani,D. Ware Branch +9 more
TL;DR: There are limitations in the quality of the data supporting the association of aPL with obstetric complications included in the current APS classification criteria and recommended treatments for all pregnancy morbidity associated to APS also lack well-designed studies to confirm its efficacy.
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Induction of endothelial cell tissue factor activity by sera from patients with antiphospholipid syndrome: a possible mechanism of thrombosis.
D. Ware Branch,George M. Rodgers +1 more
TL;DR: Endothelial cell tissue factor expression is induced by antiphospholipid sera, with activity residing at least in part in the immunoglobulin fraction.
Journal ArticleDOI
The role of monocytes in thrombotic disorders. Insights from tissue factor, monocyte-platelet aggregates and novel mechanisms.
TL;DR: This article reviews the available data on potential mechanisms that link monocytes with thrombosis-related processes and concludes that these cells are crucial for successful thrombus recanalisation.