title: Differential regulation of proinflammatory mediators following LPS- and ATP-induced activation of monocytes from patients with antiphospholipid syndrome.
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.
authors.affiliation: Department of Pathological Physiology, Faculty of Medicine and Dentistry, Palacky University, 775 20 Olomouc, Czech Republic ; Group of Molecular and Cellular Immunology, Institute of Molecular Biology, National Academy of Sciences, 0014 Yerevan, Armenia.
authors.forename: Anush
authors.initials: A
authors.lastname: Martirosyan
authors.affiliation: Department of Pathological Physiology, Faculty of Medicine and Dentistry, Palacky University, 775 20 Olomouc, Czech Republic.
authors.forename: Martin
authors.initials: M
authors.lastname: Petrek
authors.affiliation: Department of Pathological Physiology, Faculty of Medicine and Dentistry, Palacky University, 775 20 Olomouc, Czech Republic.
authors.forename: Zdenka
authors.initials: Z
authors.lastname: Navratilova
authors.affiliation: Department of Obstetrics, Institute of Perinatology, Obstetrics and Gynecology, 0078 Yerevan, Armenia.
authors.forename: Armen
authors.initials: A
authors.lastname: Blbulyan
authors.affiliation: Laboratory of Macromolecular Complexes, Institute of Molecular Biology, National Academy of Sciences, 0014 Yerevan, Armenia.
authors.forename: Anna
authors.initials: A
authors.lastname: Boyajyan
authors.affiliation: Department of Pathological Physiology, Faculty of Medicine and Dentistry, Palacky University, 775 20 Olomouc, Czech Republic ; Group of Molecular and Cellular Immunology, Institute of Molecular Biology, National Academy of Sciences, 0014 Yerevan, Armenia.
authors.forename: Gayane
authors.initials: G
authors.lastname: Manukyan
mesh_terms: D000255:Adenosine Triphosphate / Q000494:pharmacology*; D000328:Adult; D020132:Anticipation, Genetic / Q000187:drug effects; D016736:Antiphospholipid Syndrome / Q000378:metabolism*; D016022:Case-Control Studies; D018932:Chemokine CCL2 / Q000378:metabolism; D054357:Chemokine CXCL10; D005260:Female; D006801:Humans; D007249:Inflammation / Q000378:metabolism*; D007378:Interleukins / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology*; D009000:Monocytes / Q000187:drug effects* / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D050796:STAT3 Transcription Factor / Q000378:metabolism; D051195:Toll-Like Receptor 2 / Q000378:metabolism
chemical_list: C111835:CCL2 protein, human; C114753:CXCL10 protein, human; D018932:Chemokine CCL2; D054357:Chemokine CXCL10; D007378:Interleukins; D008070:Lipopolysaccharides; D012333:RNA, Messenger; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; C495342:TLR2 protein, human; D051195:Toll-Like Receptor 2; D000255:Adenosine Triphosphate