Dietary Flavonoids as Therapeutics for Preterm Birth: Luteolin and Kaempferol Suppress Inflammation in Human Gestational TissuesIn Vitro

Courtney Wall,Martha Lappas,Ratana Lim,Marin Poljak

doi:10.1155/2013/485201

Courtney Wall, Martha Lappas + Show 2 more

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https://doi.org/10.1155/2013/485201

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Abstract

Infection/inflammation is commonly associated with preterm birth (PTB), initiating uterine contractions and rupture of fetal membranes. Proinflammatory cytokines induce matrix metalloproteinases (MMPs) that degrade the extracellular matrix (ECM) and prostaglandins which initiate uterine contractions. Nuclear factor-κB (NF-κB) and activator-protein- (AP-)1 have key roles in the formation of these prolabour mediators. In nongestational tissues, dietary flavonoids such as luteolin and kaempferol inhibit NF-κB, AP-1, and their downstream targets. The aim of this study was to determine if luteolin and kaempferol reduce infection-induced prolabour mediators in human gestational tissues. Fetal membranes were incubated with LPS, and primary amnion cells and myometrial cells were incubated with IL-1β in the absence or presence of luteolin or kaempferol. Luteolin and kaempferol significantly reduced LPS-induced secretion of proinflammatory cytokines (IL-6 and IL-8) and prostaglandins (PGE2 and PGF2α) in fetal membranes, IL-1β-induced COX-2 gene expression and prostaglandin production in myometrium, and IL-1β-induced MMP-9 activity in amnion and myometrial cells. Luteolin and kaempferol decreased IL-1β-induced NF-κB p65 DNA binding activity and nuclear c-Jun expression. In conclusion, luteolin and kaempferol inhibit prolabour mediators in human gestational tissues. Given the central role of inflammation in provoking preterm labour, phytophenols may be a therapeutic approach to reduce the incidence of PTB.

Highlights

Preterm birth (PTB) is the single most important complication contributing to poor pregnancy and neonatal outcome, globally, being defined as childbirth occurring at less than 37week gestation
Luteolin and kaempferol were found to act via the Nuclear factor-κB (NF-κB) and AP-1 pathways, inhibiting NF-κB p65 DNA binding activity and nuclear c-Jun expression in myometrial cells
We used human fetal membranes and myometrial cells to determine the effect of luteolin and kaempferol on LPS or IL-1β-induced expression and release of the proinflammatory cytokines TNF-α, IL-6, and IL-8

Summary

Introduction

Preterm birth (PTB) is the single most important complication contributing to poor pregnancy and neonatal outcome, globally, being defined as childbirth occurring at less than 37week gestation. Infection activates the maternal immune system, which causes production of the proinflammatory cytokines IL-1β and TNF-α. They bind to their respective receptors located on placenta, fetal membranes, and myometrium to induce the activity of the proinflammatory and prolabour transcription factors activatorprotein- (AP-) and nuclear factor kappa B (NF-κB) [6,7,8,9]. AP-1 and NF-κB upregulate transcription of proteases, prostaglandins, and cytokines which lead to delivery of the baby by causing cervical ripening, rupture of fetal membranes, and uterine contractions, three critical stages in the initiation of labour

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