Lipopolysaccharide enhances the transcription of prostaglandin H synthase-2 gene in primary human trophoblasts

Anteby, Eyal Y.; Johnson, Roger D.; Huang, Xiahoua; Dryden, Damla K.; Nelson, D. Michael; Sadovsky, Yoel

doi:10.1016/s0002-9378(98)70422-3

Cited by 17 publications

(3 citation statements)

References 18 publications

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“…In studies exploring the mechanisms of preterm labor caused by microbial infections, lipopolysaccharide (LPS) has been often used as a bacterial pathogen model (3, 5). Humans are constantly exposed to low levels of LPS through microbial infections.…”

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confidence: 99%

Attenuation of Lipopolysaccharide-Induced Inflammatory Response and Phospholipids Metabolism at the Feto-Maternal Interface by N-Acetyl Cysteine

Paintlia

Singh

et al. 2008

Pediatr Res

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Maternal microbial infections cause adverse fetal developmental outcomes including embryonic resorption, intrauterine fetal death, and preterm labor. Recent studies demonstrated that oxidativestress plays an important role in chorioamniotitis pathogenesis. Herein we investigated the effect of N-acetyl cysteine (NAC) on lipopolysaccharide (LPS)-induced preterm labor and fetal demise in murine model. Lipopolysaccharide exposure at embryonic day 18 demonstrated an increase in the abortion rate and fetal demise in pregnant rats. This was associated with increase in an inflammatory response (cytokines, chemokines, and iNOS expression) and infiltration of leukocytes (monocytes and polymorphonuclear cells) in the placenta. There was increased expression of cytosolic and secretary phospholipase A2 with increased secretion of prostaglandin-2 and leukotriene B4 in the placenta, suggestive of increased metabolism of phospholipids. In addition, expression of cycloxygenase-2 and malondialdehyde production (oxidative-stress marker) was increased in the placenta. Conversely, NAC pretreatment abolished these effects of LPS in the placenta. Collectively, these data provide evidence that LPS-induced increased inflammation and metabolism of phospholipids at the feto-maternal interface (placenta) is critical for preterm labor and fetal demise during maternal microbial infections which could be blocked by antioxidant-based therapies. (Pediatr Res 64: [334][335][336][337][338][339] 2008)

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confidence: 99%

Attenuation of Lipopolysaccharide-Induced Inflammatory Response and Phospholipids Metabolism at the Feto-Maternal Interface by N-Acetyl Cysteine

Paintlia

Singh

et al. 2008

Pediatr Res

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“…It is generally not detected in most tissues but can be found in large amounts in macrophages and other inflammatory cell types following exposure to cytokines, growth factors, and mitogens. Both COX-1 and -2 are expressed in the uterus and extraembryonic membranes (35,42), and COX-2 promoter activity increases in human trophoblasts after lipopolysaccharide (LPS) exposure (1).…”

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confidence: 99%

Inhibition of cyclooxygenase-2 prevents inflammation-mediated preterm labor in the mouse

Gross¹,

Imamura

Vogt

et al. 2000

American Journal of Physiology-Regulatory, Integrative and Comp

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141

103

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Prostaglandins (PGs) have proven important during parturition, but inhibition of PG production treating preterm labor (PTL) results in significant maternal and fetal side effects. We hypothesize that specific inhibition of either cyclooxygenase (COX)-1 or -2 may result in separation of therapeutic and toxic effects. We demonstrate that COX-2, but not COX-1, is induced during inflammation-mediated PTL caused by lipopolysaccharide (LPS) administration. A two- to threefold increase in uterine and ovarian PG concentrations coincides with this induction of COX-2. The COX-2-selective inhibitor SC-236 proved effective in stopping preterm delivery and the increases in PGs. The COX-1-selective inhibitor SC-560 also attenuated uterine and ovarian PG production after LPS but did not inhibit PTL as efficiently as SC-236. COX-1-deficient mice, which show delay in the onset of term labor, exhibited no delay in onset of PTL after LPS. These findings suggest that the mechanisms for initiation of inflammation-mediated PTL and term labor differ and that selective COX-2 inhibition may provide a means of stopping inflammation-induced PTL in humans.

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“…However, the expression of both genes, for example by pro-inflammatory stimuli, still persists (DeWitt, 1991;Lyons et al, 1992;Xie et al, 1991Xie et al, , 1993. In this regard, IL-1β induced efficiently NOS-2 and COX-2 in cultured trophoblasts through a mechanism that synergizes with LPS (Anteby et al, 1998). However, TNF-α not only failed to induce NOS-2 and COX-2 expression, but decreased the actual protein levels when compared to non-stimulated cells, and lowered cell viability reflecting a cytotoxic action of this cytokine in cultured trophoblasts (microscopic observation of the cells showed characteristic morphologic alterations of apoptotic death; results not shown).…”

Section: Discussionmentioning

confidence: 99%

Requirement of nuclear factor κB for the constitutive expression of nitric oxide synthase-2 and cyclooxygenase-2 in rat trophoblasts

Callejas

Casado

Boscá

et al. 1999

Journal of Cell Science

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Recently isolated trophoblasts express nitric oxide synthase 2 (NOS-2) and cyclooxygenase 2 (COX-2), decreasing the levels of the corresponding mRNAs when the cells were maintained in culture. The sustained expression of COX-2 and NOS-2 in trophoblasts was dependent on the activation of nuclear factor kappaB (NF-kappaB) since proteasome inhibitors and antioxidants that abrogated NF-kappaB activity suppressed the induction of both genes. The time-dependent fall of the mRNA levels of NOS-2 and COX-2 paralleled the inhibition of NF-kappaB, determined by electrophoretic mobility shift assays, and the increase of the IkappaBalpha and IkappaBbeta inhibitory proteins. Isolated trophoblasts synthesized reactive oxygen intermediates (ROI), a process impaired after culturing the cells, and that might be involved in the NF-kappaB activation process. Moreover, treatment of recently isolated cells with ROI scavengers suppressed the expression of COX-2 and NOS-2. Challenge of trophoblasts with interleukin-1beta up-regulated the expression of both proteins, an effect that was potentiated by lipopolysaccharide. These results indicate that the physiological expression of NOS-2 and COX-2 in trophoblasts involves a sustained activation of NF-kappaB which inhibition abrogates the inducibility of both genes.

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Lipopolysaccharide enhances the transcription of prostaglandin H synthase-2 gene in primary human trophoblasts

Cited by 17 publications

References 18 publications

Attenuation of Lipopolysaccharide-Induced Inflammatory Response and Phospholipids Metabolism at the Feto-Maternal Interface by N-Acetyl Cysteine

Attenuation of Lipopolysaccharide-Induced Inflammatory Response and Phospholipids Metabolism at the Feto-Maternal Interface by N-Acetyl Cysteine

Inhibition of cyclooxygenase-2 prevents inflammation-mediated preterm labor in the mouse

Requirement of nuclear factor κB for the constitutive expression of nitric oxide synthase-2 and cyclooxygenase-2 in rat trophoblasts

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