Autophagy, which is decreased in labouring fetal membranes, regulates IL-1β production via the inflammasome. Issue 12 (December 2015)

• Record Type: Journal Article
• Authors: Brickle, Amelia; Tran, Ha Thi; Lim, Ratana; Liong, Stella; Lappas, Martha
• Is Part Of: Placenta. Volume 36:Issue 12(2015:Dec.)
• Page Start: 1393
• Page End: 1404
• Publication Date: 2015-12
• Subjects: Autophagy -- Fetal membranes -- Inflammasome -- Human labour -- Membrane rupture; Placenta -- Periodicals; Reproduction -- Periodicals; Placenta -- Periodicals; Placenta -- Périodiques; Reproduction -- Périodiques; 612.63
• DOI: 10.1016/j.placenta.2015.10.015
• Languages: English
• ISSNs: 0143-4004

Abstract

Abstract: Introduction: IL-1β plays a vital role in the terminal processes of human labour and delivery. Inflammasome activation is required to process pro IL-1β to an active, secreted molecule. Recent studies have shown that autophagy regulates IL-1β via the inflammasome. The aims were to determine the effect of (i) human spontaneous term and preterm labour on the expression of autophagy proteins in fetal membranes; and (ii) autophagy inhibition on IL-1β release. Methods: Fetal membranes, from term and preterm, were obtained from non-labouring and labouring women. Tissue explants were used to determine the effect of inhibition of autophagy on IL-1β secretion. Results: Expression of the autophagy proteins Beclin-1, Atg3, Atg5, Atg7, Atg12, Atg16L1 were lower after spontaneous term labour. Beclin-1 and Atg7 expression were lower after spontaneous preterm labour. Beclin-1, Atg3, and Atg7 expression were lower after preterm pre-labour rupture of membranes (PPROM) compared to preterm with intact membranes. LC3B-I expression was higher after spontaneous term and preterm labour and with PPROM; there was no difference in LC3B-II expression between the two groups. The autophagy inhibitor LY290042 increased IL-1β secretion in the presence of bacterial endotoxin LPS; IL-1β secretion was ameliorated in the presence inflammasome inhibitors. Discussion: Autophagy is decreased in fetal membranes after spontaneous labour and delivery, and PPROM. Inhibition of autophagy regulates the secretion of IL-1β via inflammasome activation. IL-1β is a major contributor to the pathophysiology of spontaneous preterm birth. Therefore activation of autophagy may be a potential therapeutic mechanism to delay or prevent infection-induced preterm birth. Highlights: Expression of autophagy proteins are decreased in fetal membranes after spontaneous term labour. Expression of autophagy proteins are decreased in fetal membranes after spontaneous preterm labour. Autophagy protein expression is lower after preterm pre-labour rupture of membranes. Inhibition of autophagy increases the secretion of IL-1β via inflammasome activation.