Cannabinoids stimulate prostaglandin production by human gestational tissues through a tissue- and CB1-receptor-specific mechanism.

Endocannabinoids have been implicated in the mechanisms of implantation, maintenance of pregnancy, and parturition in women. Intrauterine prostaglandin production and actions are also critical in each of these mechanisms. Hence, we have evaluated the effects of cannabinoids on prostaglandin biosynthesis by human gestational membranes.

Contact paracrine inhibitory networks within human gestational tissues.

We have determined the effects of separating chorion from decidua on the production of cytokines and prostaglandins. Chorionic production always exceeded that of decidua. Production rates were significantly greater in separated explants compared with intact choriodecidua, which suggests a potential contact paracrine inhibitory network.

Preferential production of prostaglandin D2 by lipopolysaccharide stimulated human choriodecidual explants.

It has been postulated that the progression of a pregnancy to term is, in part, the result of a relative maternal Th2 immunological state. Prostaglandins (PG) are critical mediators throughout pregnancy. Recent studies have demonstrated that one PG, PGD2, may be a mediator of a Th2 immunological state.

Gestational age-dependent up-regulation of prostaglandin D synthase (PGDS) and production of PGDS-derived antiinflammatory prostaglandins in human placenta.

Context: The importance of prostaglandin (PG) signaling pathways to the maintenance of pregnancy and initiation of labor is well recognized. However, the complexity of these pathways and the mechanism(s) of their coordinated regulation in physiological and pathological conditions are only now being appreciated.

Objectives: In this report we provide new evidence of a complete pathway for the biosynthesis and actions of PGD(2) and its metabolites within human gestational tissues.

Molecular inhibition of histone deacetylation results in major enhancement of the production of IL-1beta in response to LPS.

It has been postulated that the progression of human pregnancy to term is, in part, the result of a relative maternal Th(2) immunological state. This can be activated in some cell types by modifying DNA methylation and histone acetylation status. We demonstrate that the molecular inhibition of histone deacetylation, using trichostatin A (TSA), in human choriodecidual explants leads to a massive increase in lipopolysaccharide (LPS)-stimulated IL-1beta.

Misidentification of prostamides as prostaglandins.

Prostaglandins and endogenous cannabinoid metabolites share the same lipid backbone with differing polar head groups at exactly the position through which a large molecule is attached to provide antigenicity and thus raise antisera. Hence, we hypothesized that antisera raised against prostaglandins linked to a large molecule such as BSA at the carboxyl functional group would also recognize endogenous cannabinoid metabolites and lead to highly misleading interpretations of data. We found major cross-reactivity of commercial antisera raised to prostaglandins with endocannabinoid metabolites.

Identification of 9alpha,11beta-prostaglandin F2 in human amniotic fluid and characterization of its production by human gestational tissues.

Context: 9alpha,11beta-Prostaglandin F(2) (9alpha,11beta-PGF(2)) can contract uterine smooth muscle with a potency equal to PGF(2alpha). Its presence in the human uterus and production by human gestational tissues is unknown.

Objective: These studies were performed to determine whether the PGD(2)-derived 9alpha,11beta-PGF(2) is both present in human amniotic fluid and synthesized by human gestational tissues and if so, whether labor-related substances could regulate its production.

Differential effects of serum constituents on apoptosis induced by the cyclopentenone prostaglandin 15-deoxy-delta12,14-prostaglandin J2 in WISH epithelial cells.

Cyclopentenone prostaglandins, delta12-PGJ2 and 15d-PGJ2, have potent anti-tumour and anti-inflammatory activities, and have been shown to induce apoptosis in amnion-derived WISH cells. In this study, we have investigated the protective effects of serum and its constituents (growth factors and albumin) on delta12-PGJ2 and 15d-PGJ2-induced apoptosis in WISH cells. Serum (0.

Macrophage inhibitory cytokine 1 in fetal membranes and amniotic fluid from pregnancies with and without preterm labour and premature rupture of membranes.

The placenta and fetal membranes are the site of expression of macrophage inhibitory cytokine (MIC-1), a member of the transforming growth factor (TGF)-beta superfamily. We hypothesized that MIC-1 may act as an immune regulator in pregnancy complications associated with intrauterine inflammation. Decidual cells, chorionic trophoblasts and amnion epithelial cells were identified by immunohistochemistry as the predominant MIC-1-containing cell type in term membranes.

Hypothermia suppresses inducible nitric oxide synthase and stimulates cyclooxygenase-2 in lipopolysaccharide stimulated BV-2 cells.

Hypothermia is neuroprotective, possibly through suppression of microglial activation. We investigated the effects of hypothermia on lipopolysaccharide (LPS) stimulated BV-2 cells. At 37 degrees C, LPS elicited strong increases in inducible nitric oxide synthase (iNOS), nitric oxide (NO), cyclooxygenase-2 (COX-2), tumour necrosis factor-alpha (TNF-alpha), and interleukin-6 (IL-6), accompanied by translocation of nuclear factor-kappaB (NF-kappaB) to the nucleus.

Critical paracrine interactions between TNF-alpha and IL-10 regulate lipopolysaccharide-stimulated human choriodecidual cytokine and prostaglandin E2 production.

Increased production of PGs by gestational membranes is believed to be a principal initiator of term and preterm labor. Intrauterine infection is associated with an inflammatory response in the choriodecidua characterized by elevated production of cytokines and PGs. The precise physiological significance of enhanced choriodecidual cytokine production in the mechanism of preterm labor remains uncertain.

Expression of angiogenic and neurotrophic factors in the human amnion and choriodecidua.

Objective: Our objective was to identify the novel or differential expression of growth or development associated genes in the human gestational membranes that might play roles in pregnancy or in term or preterm parturition.

Study Design: Complementary DNA arrays were probed with [alpha(33)P]dCTP-labeled-complementary DNA that was prepared from the RNA of reflected amnion and choriodecidua that represent term not-in-labor, term spontaneous labor, and preterm labor with and without chorioamnionitis (n = 4 per group). Differential expression (term not-in-labor vs term spontaneous labor or preterm labor with chorioamnionitis vs preterm labor without chorioamnionitis) was evaluated by Wilcoxon tests.

Regulation of prostaglandin production in an immortalized human myometrial cell line by cytokines and non-steroidal anti-inflammatory drugs.

Objective: To test the effect of selective and non-selective inhibitors of prostaglandin H synthase-2 (PGHS-II) on basal and cytokine-stimulated prostaglandin (PG) production by the immortalized human myometrial cell line, UTLRp16.

Study Design: UTLRp16 cells were treated with interleukin (IL)-1beta (0.1, 1, 10ng/ml) and tumor necrosis factor (TNF)-alpha (1, 3, 10ng/ml) in the presence or absence of indomethacin, etodolac, 5,5-dimethyl-3-(3-fluorophenyl)-4-(4-methylsulphonyl) phenyl-2 (5H)-furanone (DFU) or nimesulide for 16h (1.