Genome-wide analysis of Prokineticin-1-regulated genes in human term myometrium. Homo sapiens

Infiltration of human myometrium and cervix with leukocytes and formation of a pro-inflammatory environment within the uterus has been associated with the initiation of both term and preterm parturition. The mechanism regulating the onset of this pro-inflammatory cascade is not fully elucidated. We demonstrate that prokineticin 1 (PROK1) is up-regulated in human myometrium and placenta during labour. Gene array analysis identified 65 genes up-regulated by PROK1 in human myometrium, mainly cytokines and chemokines including: Interleukin-1beta (IL1B), chemokine C-C motif ligand 3 (CCL3) and Colony Stimulating Factor 3 (CSF3). We additionally demonstrate that PROK1 increases expression of chemokines C-C motif ligand 20 (CCL20), Interleukin-6 (IL-6), Interleukin-8 (IL-8), prostaglandin synthase 2 (PTGS2) and prostaglandin E2 and F2α secretion. We propose that PROK1 is a novel inflammatory mediator that can contribute to onset of human parturition at term and partially mediate premature onset of inflammatory pathways during bacterial infection. Overall design: Total RNA was extracted from human term non-labour myometrium explants treated with prokineticin for 6 and 24 hours compared to vehicle-treated explants. Six biological replicates were analyzed for each treatment and time point. Two of the 6-hour vehicle samples failed a quality-control analysis and were substituted with a 4-hour vehicle treatment from the same tissue sample in each case.