Evidence for Interleukin‐10‐Mediated Inhibition of Cyclo‐ oxygenase‐2 Expression and Prostaglandin Production in Preterm Human Placenta
Interleukin-10 (IL-10) is thought to be a key cytokine for the maintenance of pregnancy. Here we examined the expression profiles of IL-10 and cyclo-oxygenase-2 (COX-2), and the effect of IL-10 on COX-2 expression and prostaglandin release in the human placenta from preterm labor deliveries associated with chorioamnionitis.
Placental tissues from preterm labor and term labor deliveries were processed for ex vivo placental explant culture system. IL-10 expression was assessed by enzyme-linked immunosorbent assay (ELISA) and immunohistochemical (IHC) analysis. COX-2 expression was evaluated by IHC, Western blotting and reverse transcriptase-polymerase chain reaction. Prostaglandin E2 (PGE2) release was measured by ELISA.
IL-10 was significantly reduced in chorioamnionitis-associated preterm labor as well as in term labor placental tissues compared with second trimester normal pregnancy samples obtained from elective terminations. Similar results were obtained with freshly isolated cytotrophoblasts from these deliveries. As expected, COX-2 mRNA was detected at significant levels in tissues from term and preterm labor deliveries compared with no labor term deliveries. Importantly, IL-10 inhibited COX-2 expression in cultured placental explants from preterm labor deliveries, but not from term labor samples. Inhibition of COX-2 expression coincided with reduced PGE2 release.
These results demonstrate the importance of IL-10 in countering inflammation associated with preterm labor, and suggest that term and preterm parturition may, in part, represent different conditions.
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Available from: Ronald F Lamont
- "Anti-infl ammatory cytokines contribute to the onset of SPTL by downregulation or cessation of activity. IL-10 is the key anti-infl ammatory cytokine for the maintenance of pregnancy, the downregulation of which is central to the onset of normal labour (Hanna et al. 2000) and it is reduced in SPTL (Blanco-Quiros et al. 2000; Hanna et al. 2006). IL-10 inhibits the activation of T cells, monocytes and macrophages and has potent immunosuppressive activity by inhibiting both IL-12 and IFN-γ synthesis and hence maintenance of the pregnancy (Moore et al. 1993). "
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ABSTRACT: Spontaneous preterm labour and delivery is a syndrome comprising diverse pathological pathways that result in labour and delivery before term. It is recognised that multiple pathological processes are involved, and infection has been well studied and firmly established as a cause. Although the molecular mechanisms responsible for this process have been identified, there is a lack of consensus about effective antibiotic intervention. Systematic reviews of the few well conducted studies suggest that antibiotics active against bacterial vaginosis or related organisms (clindamycin) given to appropriate women (those with objective evidence of abnormal genital tract flora), and used early in pregnancy (< 22 completed weeks of gestation) before irreversible inflammatory damage occurs, can reduce the rate of preterm birth. There is a need for well constructed trials to understand the vaginal microbiome and how the different types of maternal immune response influences outcome.
Journal of Obstetrics and Gynaecology 11/2013; 33(8):768-75. DOI:10.3109/01443615.2013.842963 · 0.55 Impact Factor
Available from: Steven W Threlkeld
- "Cytokines are also critical in interactions between the maternal immune and reproductive systems and in establishing and maintaining pregnancy (Hanna et al., 2000, 2006; Hill, 1992; Makhseed et al., 2000; Thaxton and Sharma, 2010; Wegmann et al., 1993). Both IL-1␤ and IL-6 synthesis has been documented in human placenta and placental cytokine expression changes in a gestational age-dependent manner (Hanna et al., 2000, 2006; Hu et al., 1992; Kameda et al., 1990). However, maternal brain cytokine expression has not been examined, to the best of our knowledge, in any species during advancing gestation. "
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ABSTRACT: Interleukin (IL)-1β and IL-6 have been implicated in brain development, injury progression, and fetal/maternal immune interactions. We examined IL-1β and IL-6 protein expression in cerebral cortex (CC) and white matter (WM) from non-ischemic ovine fetuses at 87-90, 122-127, and 135-137 days of gestation, pregnant ewes at 87-90 and 135-137 days of gestation, and fetuses exposed to 48 or 72h of reperfusion after ischemia. Protein expression was determined by Western immunoblot. In non-ischemic CC, IL-1β was higher (P<0.05) in adult sheep and fetuses at 135-137 than 87-90 and 122-127 days, and IL-6 higher at 122-127 than 87-90 days, and in adults than fetuses at 87-90, 122-127, and 135-137 days of gestation. In non-ischemic fetal WM, IL-6 was higher at 135-137 than 87-90 days, but IL-1β did not differ. In CC, IL-1β was higher in ewes at 135-137 than 87-90 days and IL-6 at 135-137 days and in non-pregnant adults than ewes at 87-90 days of gestation. In WM, IL-1β was higher in ewes at 135-137 than 87-90 days of gestation, but IL-6 did not differ. Forty-eight and 72h after ischemia, CC IL-1β was higher than in non-ischemic fetuses. Seventy-two hours after ischemia, IL-1β and IL-6 were higher in WM than CC. In conclusion, IL-1β and IL-6 exhibit developmental regulation in fetal brain, change during gestation in brains of pregnant ewes, show regional differences in normal brains of fetuses and ewes, demonstrate differential responses after ischemia in CC and WM, and IL-1β but not IL-6 increases after ischemia in CC.
International journal of developmental neuroscience: the official journal of the International Society for Developmental Neuroscience 06/2012; 30(6):457-63. DOI:10.1016/j.ijdevneu.2012.06.001 · 2.58 Impact Factor
Available from: Demba Sarr
- "Along the same lines, IL-10 mRNA was significantly higher in infected placentas compared to uninfected ones, as previously described [40,41]. High level of IL-10 could be deleterious, as IL-10 is known to inhibit COX-2 expression in preterm human placenta  and secretion of inflammatory cytokines by monocytes . It was also associated with high parasitaemia, severe anaemia and a low level of COX-2 in PBMC [8,22]. "
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ABSTRACT: Placental malaria (PM) is associated with poor foetal development, but the pathophysiological processes involved are poorly understood. Cyclooxygenase (COX) and lipoxygenase (LOX) which convert fatty acids to prostaglandins and leukotrienes, play important roles in pregnancy and foetal development. COX-2, currently targeted by specific drugs, plays a dual role as it associates with both pre-eclampsia pathology and recovery during infection. The role of COX during PM was questioned by quantifying at delivery COX-1, COX-2, 15-LOX, and IL-10 expression in two groups of malaria infected and uninfected placenta.
Placental biopsies were collected at delivery for mRNA isolation and quantification, using real time PCR.
COX-2 and IL-10 mRNAs increased mainly during chronic infections (nine- and five-times, respectively), whereas COX-1 transcripts remained constant. COX-2 over-expression was associated with a higher birth weight of the baby, but with a lower rate of haemoglobin of the mother. It was associated with a macrophage infiltration of the placenta and with a low haemozoin infiltration. In the opposite way, placental infection was associated with lower expression of 15-LOX mRNA. A high degree of haemozoin deposition correlates with low birth weight and decreased expression of COX-2.
These data provide evidence that COX-2 and IL-10 are highly induced during chronic infection of the placenta, but were not associated with preterm delivery or low birth weight. The data support the involvement of COX-2 in the recovery phase of the placental infection.
Malaria Journal 02/2010; 9(1):45. DOI:10.1186/1475-2875-9-45 · 3.11 Impact Factor
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