Evidence for Interleukin‐10‐Mediated Inhibition of Cyclo‐ oxygenase‐2 Expression and Prostaglandin Production in Preterm Human Placenta

Department of Pediatrics/Neonatology, UMDNJ-Robert Wood Johnson Medical School, New Brunswick, NJ, USA.
American journal of reproductive immunology (New York, N.Y.: 1989) (Impact Factor: 2.44). 02/2006; 55(1):19-27. DOI: 10.1111/j.1600-0897.2005.00342.x
Source: PubMed


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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    • "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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    • "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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    • "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 [42] and secretion of inflammatory cytokines by monocytes [43]. It was also associated with high parasitaemia, severe anaemia and a low level of COX-2 in PBMC [8,22]. "
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