Progranulin (PGRN) is an anti-inflammatory molecule involved in a variety of biological phenomena, but its expression in the cervix and anti-inflammatory effects remain unclear. We investigated the dynamics of PGRN during pregnancy and its anti-inflammatory effect on the cervix. This study was conducted under the approval of the institutional ethics committee. In 36 mothers, PGRN concentrations in serum at mid- and late-term pregnancy and postpartum and in cervical mucus before delivery were measured by ELISA. The effects of estradiol and progesterone administration on PGRN expression were examined in a cervical cell line by real-time PCR. The effect of TNF-α administration followed by PGRN on suppression of inflammatory cytokines was examined. We examined the anti-inflammatory effect in the cervix when PGRN was administered to the cervix using a preterm mouse model. Serum PGRN concentrations in late pregnancy were predominantly higher than those in midpregnancy and postpartum. A significant negative correlation was found between PGRN concentration in cervical mucus and Bishop score before labor onset (r2=0.47 p<0.01). In the cervical cell line, PGRN expression was enhanced by P4 stimulation. PGRN treatment in cervical cells showed a predominant suppression of inflammatory cytokines (IL1β, IL-6, and IL-8) induced by TNF-α. In the preterm mouse model, induction of IL1β in the cervix was predominantly suppressed by PGRN treatment. These results suggest that PGRN expression is upregulated during pregnancy under the influence of P4 and that PGRN in the cervix plays an important role in regulating cervical ripening through its anti-inflammatory effect.
