De novo ceramide synthesis is involved in acute inflammation during labor

Abstract

Gestation is regulated by an inflammatory process that allows implantation and parturition. The comprehension of such inflammatory switches is important for the identification of therapeutic targets in pregnancy defects. Sphingolipids are a class of structural membrane components with important signaling functions. Among sphingolipids, ceramide is a well-known mediator of stress signals and pro-inflammatory responses. In this paper, we evaluated the association between ceramide increase and the inflammatory process of labor, comparing placentas from vaginal deliveries, including both spontaneous and induced labor, versus elective cesarean. We demonstrated that: (i) the inflammatory marker IL-6 is upregulated in labored placentas; (ii) IL-6 content inversely correlates with labor duration; (iii) ceramide content and expression of serine palmitoyl transferase (SPT, rate limiting enzyme for de novo ceramide synthesis) are increased in labored placentas; (iv) the expression of SPT directly correlates with inflammation and inversely with labor duration. These observations suggest that ceramide metabolism and signaling may be implicated in controlling important inflammatory mechanisms driving gestation: we hypothesize that ceramide can be a therapeutic target in inflammatory complications of parturition.

Metabolite Changes in Maternal and Fetal Plasma Following Spontaneous Labour at Term in Humans Using Untargeted Metabolomics Analysis: A Pilot Study

“…This finding supports previous reports of increased ceramide levels and expression of serine palmitoyl transferase, the rate-limiting enzyme for ceramide synthesis de novo , in the placentas of women who laboured compared with those who delivered by elective CS. This group also reported an increase in interleukin-6, suggesting the involvement of ceramide signalling and inflammatory mechanisms in labour [46]. Our data support the view that the endocannabinoid/ceramide/sphingolipid pathway has the potential to stimulate labour [40,42,46].…”

“…This group also reported an increase in interleukin-6, suggesting the involvement of ceramide signalling and inflammatory mechanisms in labour [46]. Our data support the view that the endocannabinoid/ceramide/sphingolipid pathway has the potential to stimulate labour [40,42,46].…”

Sphingolipid Signature of Human Feto-Placental Vasculature in Preeclampsia

“…Furthermore, the expression of key enzymes involved in the sphingolipid de novo biosynthesis, SPTLC1 and SPTLC2, were significantly increased, as reported in inflammatory and hypertensive [29,64,65]. Accordingly, we found a significant upregulation of SPT activity in chorionic arteries of PE compared to healthy subjects.…”

Brain Cancer-Activated Microglia: A Potential Role for Sphingolipids

“…It has already been demonstrated in different diseases that Cer plays a pro-inflammatory role in, for instance, airway inflammation, pulmonary edema, inflammatory bowel disease, inflammation during labor, post myocardium ischemic and cystic fibrosis [159][160][161][162][163][164][165][166][167][168]. But, the role of SLs in microglia was depicted only a few years ago when Jung and colleagues [162] showed that Cer with acyl chain length C2 to C8 was able to block the inflammation induced by LPS.…”