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 alpha-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-1alpha and IL-1beta 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-1alpha and IL-1beta 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.
Naldini
Antonella
A
Department of Physiology, University of Siena, Siena, Italy. naldini@Unisi.it
Pucci
Annalisa
A
Carney
Darrell H
DH
Fanetti
Giuseppe
G
Carraro
Fabio
F
D006801:Humans; D007375:Interleukin-1 / Q000096:biosynthesis / Q000235:genetics*; D007963:Leukocytes, Mononuclear / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D044463:Receptor, PAR-1; D018179:Receptors, Thrombin / Q000378:metabolism*; D013917:Thrombin / Q000378:metabolism*; D015854:Up-Regulation
D007375:Interleukin-1; D012333:RNA, Messenger; D044463:Receptor, PAR-1; D018179:Receptors, Thrombin; D013917:Thrombin