Mechanism of tissue factor production by monocytes stimulated with neutrophil elastase
| Autor: | Manabu Aoki, Yasuo Yamaguchi, Tomomichi Ono, Katsurou Sagara, Yasuji Ishimaru, Jin Kawata, Eiji Hirose, Shinji Narahara, Tamami Matsmoto |
|---|---|
| Rok vydání: | 2015 |
| Předmět: |
Indoles
Pyridines medicine.drug_class Primary Cell Culture Carbazoles p38 Mitogen-Activated Protein Kinases Monocytes Thromboplastin Maleimides Tissue factor Gallic Acid medicine Humans Staurosporine RNA Messenger Enzyme Inhibitors Estrenes Protein Kinase Inhibitors Molecular Biology Protein Kinase C Protein kinase C Flavonoids biology Phospholipase C Chemistry Monocyte Elastase Imidazoles Cell Biology Hematology Protein kinase inhibitor Calcium Channel Blockers Molecular biology Pyrrolidinones medicine.anatomical_structure Gene Expression Regulation Type C Phospholipases Neutrophil elastase biology.protein Molecular Medicine Leukocyte Elastase Signal Transduction medicine.drug |
| Zdroj: | Blood Cells, Molecules, and Diseases. 54:206-209 |
| ISSN: | 1079-9796 |
| DOI: | 10.1016/j.bcmd.2014.10.005 |
| Popis: | Background Monocytes and neutrophils are activated during disseminated intravascular coagulation. Tissue factor, the main initiator of coagulation, is expressed by monocytes, while elastase is released by neutrophils. Aims This study investigated tissue factor production by peripheral monocytes after stimulation with human neutrophil elastase. Methods Tissue factor mRNA levels were investigated by the reverse transcriptase-polymerase chain reaction and tissue factor protein production was assessed by western blotting when monocytes were exposed to neutrophil elastase with or without preincubation using various inhibitors. Results Neutrophil elastase upregulated tissue factor mRNA and protein levels in monocytes. Both U73122 (phospholipase C inhibitor) and TMB-8 (intracellular calcium antagonist) prevented the upregulation of tissue factor mRNA. SB203580 (p38 mitogen-activated protein kinase inhibitor) suppressed this response, but PD98059 (extracellular signal-regulated kinase inhibitor) did not. Ro-318425 (ATP-competitive and selective protein kinase C (PKC) inhibitor) and Go 6976 (inhibitor of conventional PKCs and PKCμ) blocked the upregulation of tissue factor mRNA expression. Go 6983 (broad-spectrum PKC inhibitor) and CGP 4125 (staurosporine analog) partially attenuated it, as did a PKC theta/delta inhibitor. Conclusions Neutrophil elastase mainly enhances tissue factor production by monocytes via the phospholipase C/conventional PKC/p38 MAPK pathway, although a novel PKC is also involved. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Full Text from ScienceDirect