Oxytocin activates NF-κB-mediated inflammatory pathways in human gestational tissues

Publication date: Available online 14 November 2014 Source:Molecular and Cellular Endocrinology Author(s): Sung Hye Kim , David A. MacIntyre , Maria Firmino Da Silva , Andrew M. Blanks , Yun S Lee , Steven Thornton , Phillip R. Bennett , Vasso Terzidou Human labor, both at term and preterm, is preceded by NF-κB-mediated inflammatory activation within the uterus leading to myometrial activation, fetal membrane remodelling and cervical ripening. The stimuli triggering inflammatory activation in normal human parturition are not fully understood. We show that the neurohypophyseal peptide, oxytocin (OT), activates NF-κB and stimulates downstream inflammatory pathways in human gestational tissues. OT stimulation (1pM-100nM) specifically via its receptor (OTR) in human myometrial and amnion primary cells led to MAPK and NF-κB activation within 15min and maximal p65-subunit nuclear translocation within 30min. Both in human myometrium and amnion, OT-induced activation of the canonical NF-κB pathway upregulated key inflammatory labor-associated genes including IL-8, CCL5, IL-6 and COX-2. IKKβ inhibition (TPCA1; 10µM) suppressed OT-induced NF-κB-p65 phosphorylation, whereas p65-siRNA knockdown reduced basal and OT-induced COX-2 levels in myometrium and amnion. In both gestational tissues, MEK1/2 (U0126; 10µM) or p38 inhibition (SB203580; 10µM) suppressed OT-induced COX-2 expression, but OT-induced p65-phosphorylation was only inhibited in amnion suggesting OT activa...
Source: Molecular and Cellular Endocrinology - Category: Endocrinology Source Type: research