Abstract.
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.
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Received 9 December 2007; received after revision 16 January 2008; accepted 18 January 2008
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Ostrowska, E., Reiser, G. The protease-activated receptor-3 (PAR-3) can signal autonomously to induce interleukin-8 release. Cell. Mol. Life Sci. 65, 970–981 (2008). https://doi.org/10.1007/s00018-008-7555-y
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DOI: https://doi.org/10.1007/s00018-008-7555-y