De novo ceramide synthesis is involved in acute inflammation during labor.
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.
Paola
P
Signorelli
Laura
L
Avagliano
Marta R
MR
Reforgiato
Nadia
N
Toppi
Josefina
J
Casas
Gemma
G
Fabriàs
Anna Maria
AM
Marconi
Riccardo
R
Ghidoni
Anna
A
Caretti
D000328:Adult; D002518:Ceramides / Q000096:biosynthesis*; D005260:Female; D006801:Humans; D007249:Inflammation / Q000378:metabolism*; D015850:Interleukin-6 / Q000378:metabolism; D007743:Labor, Obstetric / Q000378:metabolism*; D010920:Placenta / Q000378:metabolism / Q000473:pathology; D011247:Pregnancy; D051102:Serine C-Palmitoyltransferase / Q000096:biosynthesis / Q000378:metabolism
D002518:Ceramides; D015850:Interleukin-6; D051102:Serine C-Palmitoyltransferase