Evidence for interleukin-10-mediated inhibition of cyclo- oxygenase-2 expression and prostaglandin production in preterm human placenta.
ABSTRACT 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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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 · 0.60 Impact Factor
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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 · 2.92 Impact Factor
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ABSTRACT: Cervical ripening is a complex process of modification of cervical tissue that enables dilation of the cervix at parturition. Cervical smooth muscle tissue might play a role by contracting or by secretion of cytokines or MMPs. To assess a contractile role for the cervical smooth muscle cells in cervical dilatation, we measured cervical diameter with ultrasound cervimetry together with EMG-activity of the myometrium, cervical outer muscular layer (COML) and cervical stromal layer (CSL). This was done in 4-6 cows from the moment a PGF2alpha was injected until 48 hours after expulsion. The COML EMG activity began to increase some12 h before cervical dilatation, and decreased after fetal expulsion. The increase before and decrease after expulsion was low compared to the myometrium and not characterized by an increase and decrease in maximum EMG amplitudes. The COML showed contracture and contraction like EMG activity in unison with in the myometrium, but also irregular EMG activity. After calving, the cervical diameter measured initially 6 cm, increased during the first 15 h and decreased afterwards. Myometrial and cervical EMG burst patterns were accompanied by transient dilatations of the caudal cervix. These data suggest that the activity of the outer muscular layer of the cervix is partly differently regulated compared with the myometrium. Increased activity of the outer muscular layer could have functional relevance in the evacuation of the uterus. The CSL did not exhibit EMG activity and was further characterized. Cervical biopsies were repeatedly taken from 10 pregnant cows at days 185 and 275 of gestation, at calving and 30 days afterwards, and analysed with immuno histochemistry and RT-PCR (n=5). At parturition, the smooth muscle tissue in the CSL remained arranged in bundles but cellular density and the smooth muscle actin alpha (SMA) mRNA expressions were decreased. Additionally, the SMA staining and connexin-43 expression and staining remained constant. This might indicate that stromal smooth muscle cells are not prepared to contract with parturition. Co-expression with vimentin suggests that the stromal smooth muscle cells predominantly have a secretory function in cows. The cervical ripening process is divided in a gradual stage and a final stage which is an inflammatory process. Involvement of Matrix Metallo Proteinases (MMPs), produced by smooth muscle cells and of cytokines and leucocytes in the two stages of bovine cervical ripening were assessed in the series of cervical biopsies. MMP-2 expression had already increased at 5 days before parturition and was present in smooth muscle cells and extra cellular matrix, which suggests involvement of smooth muscle cells in collagen denaturation during gradual cervical ripening. At parturition, IL-8 expression had largely increased enabling the large invasion of neutrophils, and MMP-1 and MMP-9 protein expression were increased. Neutrophils might have contributed to cervical softening by secreting MMPs. At parturition, the levels of IL-1 only slightly increased, of IL-6 remained the same and of TNFalpha decreased, which potentially were the consequences of increased IL-10 expression. This indicates that final ripening at term parturition is a non-infectious inflammatory process influenced by regulatory cytokines.