THROMBIN ENHANCEMENT OF INTERLEUKIN-1 EXPRESSION IN MONONUCLEAR CELLS: INVOLVEMENT OF PROTEINASE-ACTIVATED RECEPTOR-1
In addition to its central role in blood coagulation and hemostasis, human α-thrombin is considered a pro-inflammatory molecule. We have previously demonstrated that differentiated monocytes express the proteolytically activated receptor for thrombin (PAR-1) and that thrombin enhances the release of...
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Published in | Cytokine (Philadelphia, Pa.) Vol. 20; no. 5; pp. 191 - 199 |
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Main Authors | , , , , |
Format | Journal Article |
Language | English |
Published |
England
Elsevier Ltd
07.12.2002
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Subjects | |
Online Access | Get full text |
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Summary: | In addition to its central role in blood coagulation and hemostasis, human α-thrombin is considered a pro-inflammatory molecule. We have previously demonstrated that differentiated monocytes express the proteolytically activated receptor for thrombin (PAR-1) and that thrombin enhances the release of interleukin (IL)-6 in human monocytes. In the present study we show that thrombin upregulates the production of both IL-1α and IL-1β in phytohemagglutin (PHA)-activated human peripheral blood mononuclear cells (PBMC). Treating PHA-activated PBMC with the PAR-1 activation peptide, SFLLRN, mimics the effects of thrombin on IL-1α and IL-1β production. Thus, it appears that these pro-inflammatory effects induced by thrombin may be mediated through activation of PAR-1. ELISA and RNase protection assays indicate that thrombin and SFLLRN peptide upregulates IL-1 expression at both protein and mRNA levels. Thrombin directly affects monocyte IL-1 expression, since treatment of differentiated U937 cells with thrombin and SFLLRN enhances IL-1 production. These results may help explain how thrombin can enhance IL-1 expression in normal tissue to initiate tissue repair and why thrombin and thrombin-like enzymes may contribute to inflammatory responses observed in several pathophysiological conditions. |
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Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 |
ISSN: | 1043-4666 1096-0023 |
DOI: | 10.1006/cyto.2002.2001 |