Interaction Between Progesterone and Interleukin-1β in Modulating Progesterone Receptor Expression and the Inflammatory Phenotype in Human Cervical Fibroblasts

Progesterone helps maintain cervical structure during pregnancy via the progesterone receptor (PR). Two PR isoforms exist, PR-A and PR-B, which have overlapping as well as isoform-specific target genes. During late gestation, leukocytes infiltrate the cervical stroma accompanied by increased cervical cytokine levels, resembling an inflammatory process. We examined interleukin (IL)-1β regulation of the expression of PR-A, PR-B, and genes governing prostaglandin synthesis in human cervical fibroblasts (HCFs). Since progesterone has been shown to exert anti-inflammatory actions, we also examined the capacity of progesterone (R5020) to ameliorate the actions of IL-1β in HCFs. Interleukin-1β induced both PR-A and PR-B mRNA in HCFs. Interleukin-1β induced a rapid and transient loss of both PR-A and PR-B protein, followed by a latent (24 hours) increase in both PR isoforms. R5020 negated the IL-1β-induced increase in PR-A and PR-B mRNA and protein as well as the rapid IL-1β-induced downregulation of nuclear PR. ...