Prokineticin-1 - a novel mediator of the inflammatory response in third trimester human placenta.
March 29th, 2008 | by admin |Prokineticin-1 - a novel mediator of the inflammatory response in third trimester human placenta.
Prokineticin-1 (PK1) is a recently described protein with a wide range of functions, including tissue specific angiogenesis, modulation of inflammatory responses and regulation of haemopoiesis. The aim of this study was to investigate the localisation and expression of PK1 and PKR1, their signalling pathways and the effect of PK1 on expression of the inflammatory mediators cyclo-oxygenase (COX)-2 and interleukin (IL)-8 in third trimester placenta. PK1 and PKR1 were highly expressed in term placenta and immunolocalised to syncytiotrophoblasts, cytotrophoblasts, fetal endothelium and macrophages. PK1 induced a time dependent increase in expression of IL-8 and COX-2, which was significantly reduced by inhibitors of Gq, cSrc, EGFR and MEK. Treatment of third trimester placenta with 40nM PK1 induced a rapid phosphorylation of cSrc, EGFR and ERK1/2. Phosphorylation of ERK1/2 in response to PK1 was dependent on sequential phosphorylation of cSrc and EGFR. Using double immunofluorescent immunohistochemistry, PKR1 co-localized with IL-8 and COX-2 in placenta. These data suggest that PK1 may have a novel role as a mediator of the inflammatory response in placenta.
Denison FC, Battersby S, King AE, Szuber M, Jabbour HN.
Department of Reproductive and Developmental Sciences, Centre for Reproductive Biology, University of Edinburgh, EH16 4SB, UK; MRC Human Reproductive Sciences Unit, Centre for Reproductive Biology, University of Edinburgh, EH16 4SB, UK.