After discovery of antiphospholipid syndrome (APS) our understanding of molecular mechanisms of living matter has become more sophisticated and on this way monocytes has become crucial player, particularly in pathogenesis of APS. Thrombotic and non-thrombotic complications of APS could be explained by monocytes' activation too. But mechanisms underlying their activation are poorly investigated. So we aimed to determine transcriptional activity of monocytes after exposing them to low concentrations of lipopolysaccharide (LPS) and LPS+ATP using comparative of RT-PCR. Our study included eleven women suffering from recurrent miscarriages and APS (mean age 30±5,6 years). Nine healthy women (mean age of 29±8,5 years) without a positive family history of APS, autoimmune diseases and thrombosis were chosen as a control group. The results showed increasing levels of TLR2, IL-23, CCL2, CXCL10, IL-1β and IL-6 in APS cells, while in healthy cells LPS resulted in IL-6 and STAT3 elevated mRNAs. Double stimulation of APS cells resulted in decreased mRNA levels of CCL-2, IL-1β, and mRNA NLRP3 in healthy cells. At the same time TLR2 mRNAs were elevated in both groups after double stimulation. Thus increased sensitivity of APS cells to LPS may contribute to thrombus formation. Low concentration of ATP diminishes LPS-induced inflammatory state of APS monocytes, which might be one of potential regulatory mechanisms.

• MeSH
• adenosintrifosfát farmakologie   MeSH
• antifosfolipidový syndrom imunologie   metabolismus   patologie   MeSH
• chemokiny krev   genetika   MeSH
• dospělí MeSH
• exprese genu MeSH
• habituální potrat imunologie   MeSH
• interleukiny krev   genetika   MeSH
• lidé MeSH
• lipopolysacharidy farmakologie   MeSH
• messenger RNA metabolismus   MeSH
• mladý dospělý MeSH
• monocyty účinky léků   imunologie   metabolismus   MeSH
• protein NLRP3 krev   genetika   MeSH
• studie případů a kontrol MeSH
• techniky in vitro MeSH
• toll-like receptor 2 krev   genetika   MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• mladý dospělý MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

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.

• MeSH
• adenosintrifosfát farmakologie   MeSH
• antifosfolipidový syndrom metabolismus   MeSH
• chemokin CCL2 metabolismus   MeSH
• chemokin CXCL10 MeSH
• dospělí MeSH
• genetická anticipace účinky léků   MeSH
• interleukiny metabolismus   MeSH
• lidé MeSH
• lipopolysacharidy farmakologie   MeSH
• messenger RNA metabolismus   MeSH
• monocyty účinky léků   metabolismus   MeSH
• studie případů a kontrol MeSH
• toll-like receptor 2 metabolismus   MeSH
• transkripční faktor STAT3 metabolismus   MeSH
• zánět metabolismus   MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH