Cooperative effects of sequential PGF2α and IL-1β on IL-6 and COX-2 expression in human myometrial cells†.
Cells, Cultured
Cyclooxygenase 2
/ genetics
Dinoprost
/ genetics
Extraembryonic Membranes
/ metabolism
Female
Gene Expression Regulation
/ physiology
Humans
Interleukin-1beta
/ genetics
Interleukin-6
/ genetics
Labor, Obstetric
/ metabolism
Myometrium
/ cytology
Pregnancy
RNA, Messenger
/ genetics
Tissue Culture Techniques
amplification
cytokines
inflammation
myometrium
parturition
prostaglandins
Journal
Biology of reproduction
ISSN: 1529-7268
Titre abrégé: Biol Reprod
Pays: United States
ID NLM: 0207224
Informations de publication
Date de publication:
01 05 2019
01 05 2019
Historique:
received:
26
06
2018
revised:
17
10
2018
accepted:
20
02
2019
pubmed:
23
2
2019
medline:
16
7
2020
entrez:
23
2
2019
Statut:
ppublish
Résumé
The change from the state of pregnancy to the state of parturition, which we call uterine transitioning, requires the actions of inflammatory mediators and results in an activated uterus capable of performing the physiology of labor. Interleukin (IL)-1β and prostaglandin (PG)F2α are two key mediators implicated in preparing the uterus for labor by regulating the expression of uterine activation proteins (UAPs) and proinflammatory cytokines and chemokines. To investigate this process, primary human myometrial smooth muscle cells (HMSMC) isolated from the lower segment of women undergoing elective cesarean sections at term (not in labor) were used to test the inflammatory cytokine and UAP outputs induced by PGF2α and IL-1β alone or in sequential combinations. PGF2α and IL-1β regulate mRNA abundance of the PGF2α receptor FP, the IL-1 receptor system, interleukin 6, and other UAPs (OXTR, COX2), driving positive feedback interactions to further amplify their own proinflammatory effects. Sequential stimulation of HMSMC by PGF2α and IL-1β in either order results in amplified upregulation of IL-6 and COX-2 mRNA and protein, compared to their effects individually. These profound increases were unique to myometrium and not observed with stimulation of human fetal membrane explants. These results suggest that PGF2α and IL-1β act cooperatively upstream in the birth cascade to maximize amplification of IL-6 and COX-2, to build inflammatory load and thereby promote uterine transition. Targeting PGF2α or IL-1β, their actions, or intermediates (e.g. IL-6) would be an effective therapeutic intervention for preterm birth prevention or delay.
Identifiants
pubmed: 30794283
pii: 5362645
doi: 10.1093/biolre/ioz029
pmc: PMC6497526
doi:
Substances chimiques
Interleukin-1beta
0
Interleukin-6
0
RNA, Messenger
0
Dinoprost
B7IN85G1HY
Cyclooxygenase 2
EC 1.14.99.1
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1370-1385Subventions
Organisme : CIHR
ID : 119513
Pays : Canada
Informations de copyright
© The Author(s) 2019. Published by Oxford University Press on behalf of Society for the Study of Reproduction.
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