THROMBIN ENHANCEMENT OF INTERLEUKIN-1 EXPRESSION IN MONONUCLEAR CELLS: INVOLVEMENT OF PROTEINASE-ACTIVATED RECEPTOR-1

• Published in: Cytokine (Philadelphia, Pa.) Vol. 20; no. 5; pp. 191 - 199
• Main Authors: Naldini, Antonella, Pucci, Annalisa, Carney, Darrell H, Fanetti, Giuseppe, Carraro, Fabio
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 07.12.2002
• Subjects: cytokine/inflammation/monocyte/sepsis/thrombin; Humans; Interleukin-1 - biosynthesis; Interleukin-1 - genetics; Leukocytes, Mononuclear - metabolism; Receptor, PAR-1; Receptors, Thrombin - metabolism; RNA, Messenger - metabolism; Thrombin - metabolism; Up-Regulation; cytokine/inflammation/monocyte/sepsis/thrombin
• ISSN: 1043-4666; 1096-0023
• DOI: 10.1006/cyto.2002.2001

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.