ORIGINAL ARTICLE: Can Sulfasalazine Prevent Infection‐Mediated Pre‐Term Birth in a Murine Model?

Nath, Carl; Ananth, Cande V.; Smulian, John C.; Peltier, Morgan R.

doi:10.1111/j.1600-0897.2009.00773.x

Cited by 22 publications

(15 citation statements)

References 47 publications

(48 reference statements)

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“…Furthermore, mouse studies have been employed to demonstrate that by inhibiting NF- κ B or AP-1, infection-induced PTB can be delayed [49, 50]. In nongestational tissues, luteolin and kaempferol are thought to exert their anti-inflammatory actions by inhibiting NF- κ B [12–15] and AP-1 [14, 16, 17].…”

Section: Discussionmentioning

confidence: 99%

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

Wall

Lim

Poljak

et al. 2013

Oxidative Medicine and Cellular Longevity

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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.

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Section: Discussionmentioning

confidence: 99%

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

Wall

Lim

Poljak

et al. 2013

Oxidative Medicine and Cellular Longevity

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“…For the experimental studies, PBDE mix was diluted 1:1000 with culture media and added to the cells to a final concentration of 2 μ M. At this concentration, PBDE-47 binds to the Aryl hydrocarbon receptor and has biological effects [20, 21]. Heat-killed bacteria were prepared as previously described [22]. E. coli strain J5 was purchased from ATCC (Manassas, VA) and cultivated in nutrient broth, concentrated by centrifugation and resuspended in culture medium.…”

Section: Methodsmentioning

confidence: 99%

Polybrominated diphenyl ethers enhance the production of proinflammatory cytokines by the placenta

et al. 2012

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Polybrominated diphenyl ether(s) (PBDE) are ubiquitous environmental contaminants that bind and cross the placenta but their effects on pregnancy outcome are unclear. It is possible that environmental contaminants increase the risk of inflammation-mediated pregnancy complications such as preterm birth by promoting a proinflammatory environment at the maternal-fetal interface. We hypothesized that PBDE would reduce IL-10 production and enhance the production of proinflammatory cytokines associated with preterm labor/birth by placental explants. Second trimester placental explants were cultured in either vehicle (control) or 2 μM PBDE mixture of congers 47, 99 and 100 for 72 h. Cultures were then stimulated with 106 CFU/ml heat-killed Escherichia coli for a final 24 h incubation and conditioned medium was harvested for quantification of cytokines and PGE2. COX-2 content and viability of the treated tissues were then quantified by tissue ELISA and MTT reduction activity, respectively. PBDE pre-treatment reduced E. coli-stimulated IL-10 production and significantly increased E. coli-stimulated IL-1β secretion. PBDE exposure also increased basal and bacteria-stimulated COX-2 expression. Basal, but not bacteria-stimulated PGE2, was also enhanced by PBDE exposure. No effect of PBDE on viability of the explants cultures was detected. In summary, pre-exposure of placental explants to congers 47, 99, and 100 enhanced the placental proinflammatory response to infection. This may increase the risk of infection-mediated preterm birth by lowering the threshold for bacteria to stimulate a proinflammatory response(s).

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“…Similarly, nuclear translocation of p65 is evident in the upper and lower segments of the uterus at term, consistent with NFkB playing a central role in the events preceding labour (Khanjani et al 2011). As further evidence supporting the importance of NFkB in the processes leading up to labour and delivery, several NFkB inhibitors SN-50, sulphasalazine and 15d-PGJ 2 have been shown to delay preterm labour in the mouse (Condon et al 2004, Pirianov et al 2009, Nath et al 2010.…”

Section: The Role Of Pgs In Inflammationmentioning

confidence: 73%

Anti-inflammatory prostaglandins for the prevention of preterm labour

et al. 2014

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Preterm birth occurs in 10-12% of pregnancies and is the primary cause of neonatal mortality and morbidity. Tocolytic therapies have long been the focus for the prevention of preterm labour, yet they do not significantly improve neonatal outcome. A direct causal link exists between infection-induced inflammation and preterm labour. As inflammation and infection are independent risk factors for poor neonatal outcome, recent research focus has been shifted towards exploring the potential for anti-inflammatory strategies. Nuclear factor kappa B (NFkB) is a transcription factor that controls the expression of many labour-associated genes including PTGS2 (COX2), prostaglandins (PGs) and the oxytocin receptor (OXTR) as well as key inflammatory genes. Targeting the inhibition of NFkB is therefore an attractive therapeutic approach for both the prevention of preterm labour and for reducing neonatal exposure to inflammation. While PGs are considered to be pro-labour and pro-inflammatory, the cyclopentenone PG 15-deoxy-D 12,14 PGJ 2 (15d-PGJ 2 ) exhibits anti-inflammatory properties via the inhibition of NFkB in human amniocytes, myocytes and peripheral blood mononuclear cells in vitro. 15d-PGJ 2 also delays inflammation-induced preterm labour in the mouse and significantly increases pup survival. This review examines the current understanding of inflammation in the context of labour and discusses how anti-inflammatory PGs may hold promise for the prevention of preterm labour and improved neonatal outcome.Reproduction (2014) 148 R29-R40

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ORIGINAL ARTICLE: Can Sulfasalazine Prevent Infection‐Mediated Pre‐Term Birth in a Murine Model?

Abstract: SASP reduced rates of pre-term delivery and improved pregnancy outcomes for mice infected with 10(4) CFU E. coli. This suggests that SASP has the potential to play a role in strategies to prevent pre-term birth in women.

Cited by 22 publications

References 47 publications

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

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

Polybrominated diphenyl ethers enhance the production of proinflammatory cytokines by the placenta

Anti-inflammatory prostaglandins for the prevention of preterm labour

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