Upregulation of tissue factor in monocytes by cleaved high molecular weight kininogen is dependent on TNF-α and IL-1β
| Autor: | Sabina T. Khan, Mohammad M. Khan, Michael Bromberg, Munir E. Khan, Megan L. Gilman, Robert W. Colman, Yuchuan Liu |
|---|---|
| Rok vydání: | 2010 |
| Předmět: |
medicine.medical_specialty
Chemokine Kininogen High-Molecular-Weight Time Factors Physiology High-molecular-weight kininogen medicine.medical_treatment Interleukin-1beta Bradykinin Monocytes Thromboplastin chemistry.chemical_compound Tissue factor Physiology (medical) Internal medicine medicine Humans RNA Messenger Cells Cultured Mitogen-Activated Protein Kinase Kinases Kininogen Dose-Response Relationship Drug biology Tumor Necrosis Factor-alpha NF-kappa B Antibodies Monoclonal Articles Molecular biology Up-Regulation Endocrinology Cytokine chemistry Chemokine secretion biology.protein Tumor necrosis factor alpha Cardiology and Cardiovascular Medicine |
| Zdroj: | American Journal of Physiology-Heart and Circulatory Physiology. 298:H652-H658 |
| ISSN: | 1522-1539 0363-6135 |
| DOI: | 10.1152/ajpheart.00825.2009 |
| Popis: | Inflammatory bowel disease and arthritis are associated with contact activation that results in cleavage of kininogen to form high molecular weight kininogen (HKa) and bradykinin. We have previously demonstrated that HKa can stimulate inflammatory cytokine and chemokine secretion from human monocytes. We now show that HKa can upregulate tissue factor antigen and procoagulant activity on human monocytes as a function of time (1-4 h) and HKa concentration (75-900 nM). The amino acid sequence responsible to block HKa effects is G440-H455. The HKa receptor macrophage-1 (Mac-1; CD11b18) is the binding site as shown by inhibition by a monoclonal antibody to CD11b/18. Chemical inhibitors of JNK, ERK, and p38 signaling pathways block cell signaling, as does an inhibitor to the transcription factor NF-kappaB. A combination of monoclonal antibodies to TNF-alpha and IL-1beta but neither alone inhibited the HKa induction of tissue factor. These results suggest that HKa mimics LPS by triggering a paracrine pathway in monocytes that depends on TNF-alpha and IL-1beta. Antibodies to kininogen or peptidomimetics might be a useful and safe therapy in inflammatory diseases or sepsis involving cytokines. |
| Databáze: | OpenAIRE |
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