The protease-activated receptor-3 (PAR-3) can signal autonomously to induce interleukin-8 release.
Protease-activated receptors (PARs) play a clear role in the burst of inflammatory reactions and immune responses. However, for PAR-3, the most elusive member of the PAR family, the functional role is still largely unclear. It has been claimed that PAR-3 does not signal autonomously, although the wide expression of human PAR-3 indicates its important physiological roles. We demonstrate that in HEK-293 cells, stably transfected with human PAR-3, thrombin induced calcium signaling, IL-8 gene expression and IL-8 release. We confirmed this finding using human lung epithelial and human astrocytoma cells that express endogenous PAR-3. Moreover, thrombin exposure of HEK-293 cells resulted in ERK1/2 activation coinciding with IL-8 release. The effects of thrombin were not dependent on PAR-1 activation, as confirmed by PAR-1 gene silencing. Thus, we propose that PAR-3 is able to signal autonomously to induce IL-8 release mediated by ERK1/2 phosphorylation, which contributes actively to inflammatory responses.
Ostrowska
E
E
Medizinische Fakultät, Institut für Neurobiochemie, Otto-von-Guericke-Universität Magdeburg, Leipziger Strasse 44, Magdeburg, Germany.
Reiser
G
G
D001254:Astrocytoma / Q000235:genetics / Q000378:metabolism; D002460:Cell Line; D005786:Gene Expression Regulation; D006801:Humans; D016209:Interleukin-8 / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D019950:Mitogen-Activated Protein Kinase 1 / Q000037:antagonists & inhibitors / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000037:antagonists & inhibitors / Q000378:metabolism; D010766:Phosphorylation; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D034741:RNA, Small Interfering / Q000235:genetics; D044463:Receptor, PAR-1 / Q000235:genetics / Q000378:metabolism; D018179:Receptors, Thrombin / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D013917:Thrombin / Q000378:metabolism
D016209:Interleukin-8; D047428:Protein Kinase Inhibitors; D034741:RNA, Small Interfering; D044463:Receptor, PAR-1; D018179:Receptors, Thrombin; C105295:protease-activated receptor 3; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D013917:Thrombin