Abstract:
:Our previous study has shown that Toll-like receptor 4 (TLR4) and its signalling pathway contribute to anti-β₂-glycoprotein I/β₂-glycoprotein I (anti-β₂GPI/β₂GPI)-induced tissue factor (TF) expression in human acute monocytic leukaemia cell line THP-1 and annexin A2 (ANX2) is involved in this pathway. However, its downstream molecules have not been well explored. In this study, we have established that interleukin-1 receptor-associated kinases (IRAKs) and tumour necrosis factor receptor-associated factors (TRAFs) are crucial downstream molecules of anti-β₂GPI/β₂GPI-induced TLR4 signaling pathway in THP-1 cells and explored the potential mechanisms of their self-regulation. Treatment of THP-1 cells with anti-β₂GPI/β₂GPI complex induced IRAKs and TRAFs expression and activation. Anti-β₂GPI/β₂GPI complex firstly induced expression of IRAK4 and IRAK1, then IRAK1 phosphorylation and last IRAK3 upregulation. In addition, anti-β₂GPI/β₂GPI complex simultaneously and acutely enhanced mRNA levels of TRAF6, TRAF4 and zinc finger protein A20 (A20), while chronically increased A20 protein level. Moreover, anti-β₂GPI/β₂GPI complex-induced IRAKs and TRAFs expression and activation were attenuated by knockdown of ANX2 by infection with ANX2-specific RNA interference lentiviruses (LV-RNAi-ANX2) or by treatment with paclitaxel, which inhibits TLR4 as an antagonist of myeloid differentiation protein 2 (MD-2) ligand. Furthermore, both IRAK1/4 inhibitor and a specific proteasome inhibitor MG-132 could attenuate TRAFs expression as well as TF expression induced by anti-β₂GPI/β₂GPI complex. In conclusion, our results indicate that IRAKs and TRAFs play important roles in anti-β₂GPI/β₂GPI-stimulated TLR4/TF signaling pathway in THP-1 cells and contribute to the pathological processes of antiphospholipid syndrome (APS).
journal_name
Thromb Haemostjournal_title
Thrombosis and haemostasisauthors
Xu G,Wen H,Zhou H,Guo D,Zhou F,Chen D,Xie H,Wang T,Wang Hdoi
10.1160/TH11-04-0229subject
Has Abstractpub_date
2011-12-01 00:00:00pages
1158-69issue
6eissn
0340-6245issn
2567-689Xpii
11-04-0229journal_volume
106pub_type
杂志文章abstract::Our initial finding that CD40- and CD40 ligand (CD40L)-deficient mice displayed prolonged tail bleeding and platelet function analyzer (PFA-100) closure times prompted us to further investigate the role of the CD40-CD40L dyad in primary hemostasis and platelet function. Recombinant human soluble CD40L (rhsCD40L), chem...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:10.1160/TH04-12-0774
更新日期:2005-06-01 00:00:00
abstract::Shear stress has an established effect on mature endothelial cells, but less is known about how shear stress regulates endothelial progenitor cells (EPCs). In vitro expanded EPCs isolated from adult human blood represent a novel tool in regenerative vessel therapy. However, in vitro culturing may generate cells with u...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:10.1160/TH09-12-0854
更新日期:2010-09-01 00:00:00
abstract::Primary prevention is the key to managing a significant proportion of the burden of venous thromboembolism (VTE), defined as deep venous thrombosis (DVT) or pulmonary embolism (PE). This is because VTE may lead to sudden death or are often misdiagnosed and therefore treatment is not feasible. Primary prevention usuall...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章,评审
doi:10.1160/TH14-10-0823
更新日期:2015-06-01 00:00:00
abstract::In a prospective study, coagulation test results were compared in 137 patients with colorectal cancer (CRC) and 39 subjects with benign colorectal diseases. Prothrombin fragment 1+2 (F1+2), thrombin-antithrombin complex (TAT), and soluble fibrin (SF) were measured in plasma before and after surgery. CRC patients prese...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:
更新日期:2002-03-01 00:00:00
abstract::Since megakaryocytes are the cellular precursors of platelets we have investigated whether they share responses to platelet agonists, in particular collagen. Although previous studies have reported responses to thrombin in non-human megakaryocytes, through studies of single cell calcium responses and protein tyrosine-...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:
更新日期:1999-09-01 00:00:00
abstract::DX-9065a is an antithrombin III (AT III)-independent and selective inhibitor of activated blood coagulation factor X (FXa). We evaluated the effects of DX-9065a and warfarin on bleeding time and blood loss in rat tail transection model and on blood loss in hydrochloride (HCl)-induced rat gastrointestinal haemorrhage m...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:
更新日期:1999-05-01 00:00:00
abstract::Microvascular endothelial damage underlies the pathological changes in haemorrhagic colitis and the haemolytic uraemic syndrome (HUS) caused by enterohaemorrhagic Escherichia coli (EHEC). Shiga toxins (Stxs) are presently the best characterised EHEC virulence factors that can cause the microvascular endothelium injury...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章,评审
doi:10.1160/TH05-04-0265
更新日期:2005-08-01 00:00:00
abstract::The frequency of heterozygous protein C and protein S deficiency, detected by measuring total plasma antigen, in a group (n = 141) of young unrelated patients (less than 45 years old) with venous thrombotic disease was studied and compared to that of antithrombin III, fibrinogen, and plasminogen deficiencies. Among 91...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:
更新日期:1988-02-25 00:00:00
abstract::Among the nine ellagitannins, rugosin E was the most potent platelet aggregating agent with an EC50 of 1.5 +/- 0.1 microM in rabbit platelets and 3.2 +/- 0.1 microM in human platelets. The aggregations caused by rugosin E and ADP were inhibited by EGTA, PGE1, mepacrine, sodium nitroprusside and neomycin, but not by in...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:
更新日期:1997-03-01 00:00:00
abstract::Washed human platelets have been labeled with either 32Pi or glycerol-1-14C and the distribution of the label in the phospholipids determined. 32Pi was introduced primarily into polyphosphoinositides, i.e. di- and triphosphoinositide, whereas the label from glycerol which indicates de novo synthesis of lipid molecules...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:
更新日期:1976-04-30 00:00:00
abstract::Platelet-rich clots are inefficiently lysed by current fibrinolytic agents. Platelets contain a great deal of plasminogen activator inhibitor 1 (PAI-1), the principal endogenous inhibitor of tissue-type plasminogen activator (t-PA). We have tested whether PAI-1 resistant t-PAs would be more effective thrombolytic agen...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:
更新日期:1994-01-01 00:00:00
abstract::To assess the thrombotic risk of aprotinin in aortocoronary bypass surgery, we retrospectively analyzed the results of a trial, originally designed to compare the effects of one-year treatment with various antithrombotic drugs in the prevention of vein-graft occlusion. Graft patency at one year was assessed by angiogr...
journal_title:Thrombosis and haemostasis
pub_type: 临床试验,杂志文章,随机对照试验
doi:
更新日期:1996-01-01 00:00:00
abstract::Human tissue kallikrein-related peptidases are a family of 15 secreted serine proteases, located at chromosome 19q13.4. Most of them have been reported to be potential biomarkers for several carcinomas and other diseases. Human tissue kallikrein-related peptidase 7 (KLK7) has been purified from human stratum corneum a...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:
更新日期:2009-04-01 00:00:00
abstract::It is widely anticipated that large platelets are more reactive than small platelets. This was mainly shown in Ca2+-poor media albeit extracellular Ca2+ is utilized by platelets for activation. We determined the impact of extracellular Ca2+ on functional differences between large and small platelets in response to thr...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:10.1055/s-0040-1712447
更新日期:2020-07-01 00:00:00
abstract::A congenitally abnormal fibrinogen was isolated from blood of a young man with deep-vein thrombosis. Two other affected members of his family had three episodes of severe arterial thrombosis. The fibrinogen showed a delayed clotting by thrombin, but a normal clotting by Arvin, Reptilase, and prothrombin-staphylocoagul...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:
更新日期:1986-02-28 00:00:00
abstract::Increased fibrinogen concentration is a well known phenomenon following acute ischemic stroke. However, the natural course of this hyperfibrinogenemia is uncertain. We aimed to clarify whether it is of a transient or more persistent nature in patients who harbor an underlying morbid biology of atherothrombo-inflammati...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:10.1160/TH07-08-0484
更新日期:2008-01-01 00:00:00
abstract::Glucose intolerance, hyperinsulinaemia, dyslipoproteinaemia and multiple disturbances of haemostatic function are characteristics of young men with premature coronary artery disease. The relations between glucose, insulin and insulin propeptides, in the fasting state, and after an oral glucose load, and haemostatic fu...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:
更新日期:1995-04-01 00:00:00
abstract::Despite great efforts in stroke research, disability and recurrence rates in ischaemic stroke remain unacceptably high. To address this issue, one potential target for novel therapeutics is the glycoprotein von Willebrand factor (vWF), which increases in thrombogenicity especially under high shear rates as it bridges ...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章,评审
doi:10.1055/s-0038-1648251
更新日期:2018-06-01 00:00:00
abstract::The pathogenesis of abdominal aortic aneurysm (AAA) involves a central component of chronic inflammation which is predominantly mediated by myeloid cells. We hypothesized that the local inflammatory activity may be reflected in systemic alterations of neutrophil and monocyte populations as well as in soluble factors o...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:10.1055/s-0039-1679939
更新日期:2019-05-01 00:00:00
abstract::The optimal long-term treatment of acute venous thromboembolism (VTE) in patients with malignancy remains undefined. In particular, based on current evidence, it is uncertain whether secondary prophylaxis using standard intensity oral anticoagulant therapy is associated with higher risks of bleeding and recurrent thro...
journal_title:Thrombosis and haemostasis
pub_type: 临床试验,杂志文章,多中心研究
doi:
更新日期:2000-11-01 00:00:00
abstract::The origin and evolution of venom toxins is a mystery that has evoked much interest. We have recently shown that pseutarin C, a prothrombin activator from Pseudonaja textilis venom, is structurally and functionally similar to mammalian coagulation factor Xa-factor Va complex. Its catalytic subunit is homologous to fac...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:10.1160/TH04-11-0707
更新日期:2005-03-01 00:00:00
abstract::Activation and signaling of circulating blood and vessel wall cells, as well as their direct adhesive interactions, are critical for the regulation of vascular homeostasis related to vasomotor responses, inflammation, hemostasis, and wound repair. Under conditions of stress, inflammation, or infection the targeting an...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章,评审
doi:
更新日期:1999-08-01 00:00:00
abstract::Heparin cofactor II (HC II) is a heparin-dependent inhibitor of thrombin, distinct from antithrombin III (AT III). This study was designed to evaluate its metabolism in healthy subjects. Purified HC II was labelled with 125I by the lactoperoxidase-glucose oxidase technique. The biological activity of the HC II was unc...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:
更新日期:1985-10-30 00:00:00
abstract::Monitoring of anti-factor Xa activity is often performed during treatment with low-molecular-weight heparins (LMWHs) in pregnancy because the anticoagulant effect may decrease as pregnancy progresses, but assays for anti-factor Xa activity are unavailable in many clinical institutions caring for pregnant women. Heptes...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:10.1160/TH08-09-0560
更新日期:2009-11-01 00:00:00
abstract::Tissue factor is the primary initiator of coagulation cascade and plays an essential role in haemostasis and thrombosis. In addition, tissue factor and coagulation proteases contribute to many cellular responses via activation of protease activated receptors. The heart is an organ with high levels of constitutive tiss...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章,评审
doi:10.1160/TH14-03-0243
更新日期:2014-11-01 00:00:00
abstract:UNLABELLED:In this randomised, placebo-controlled 12-week study, sixty healthy postmenopausal women received either placebo (N = 16) or daily 2 mg micronised oestradiol, either unopposed (N = 16, E2 group) or combined with a progestagen for 14 days of each cycle (N = 28, E2+P group). RESULTS:As compared to placebo, pl...
journal_title:Thrombosis and haemostasis
pub_type: 临床试验,杂志文章,随机对照试验
doi:
更新日期:2000-01-01 00:00:00
abstract::Membrane-permeable 8-(4-chlorophenylthio)-2'-O-methyl cyclic AMP (8-pCPT-2'-O-Me-cAMP) has been shown to specifically activate cAMP-regulated Epac proteins, without direct effects on protein kinase A and protein kinase G. During isometric tension measurements in thoracic aortic rings from Wistar rats, we observed that...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:10.1160/TH09-06-0341
更新日期:2010-03-01 00:00:00
abstract::The walls of rabbit mesenteric arterioles and venules (diameter 20 to 40 microns) were punctured with glass micropipets (tip diameter 6 to 8 microns). Thromboembolic reactions resulting from this standardized, small mechanical vessel wall injury could be quantified in vivo with the use of intravital video-microscopy. ...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:
更新日期:1988-02-25 00:00:00
abstract::Individuals with lupus anticoagulants (LA) are at risk for thromboembolism (TE). Chronic inflammation is an important characteristic in LA patients which may dispose for TE. Platelets play a key role in inflammation and TE. We therefore investigated gene polymorphisms as well as plasma levels of platelet receptors as ...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:
更新日期:2007-04-01 00:00:00
abstract::Fibrin(ogen) is the major matrix ligand for beta3 integrins. If alpha(v)beta3 is the major receptor for fibrin(ogen) on intimal smooth muscle cells, we might expect to see this integrin associated with fibrin(ogen). Eighty-four specimens obtained from endarterectomies of 14 patients were studied. Fibrin was frequently...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:
更新日期:2000-08-01 00:00:00