Prostaglandins (PGs) are lipid mediators that participate in the regulation of immunological and inflammatory responses, and PG production can affect viral replication. In this study, we have investigated the mechanism of PGE2 production in airway epithelial cells, following respiratory syncytial virus (RSV) infection, and its role in viral replication. We show that RSV infection strongly induces PGE2 secretion, in a time- and replication-dependent manner, through increased cyclooxygenase-2 (COX-2) expression, which occurs independently from viral or cellular protein synthesis. RSV infection induces arachidonic acid release through induction of cytoplasmic phospholipase A2 (cPLA2) enzymatic activity and its membrane translocation. Specific inhibitors of cPLA2 significantly block RSV-induced PGE2 secretion, indicating a key role of cPLA2 in viral-induced PG production. Blocking PG secretion, through cPLA2 or COX-2 inhibition, results in impairment of RSV replication and subsequent RSV-mediated epithelial cell responses, suggesting that inhibition of PG secretion could be beneficial in RSV infection by reducing proinflammatory mediator production.

Two diets simulating the recommendations of the American Heart Association to increase the intake of n-3 polyunsaturated fatty acids (n-3 PUFAs) were tested on Golden Syrian hamsters and compared to the diet simulating the current estimated consumption of fat in the United States. N-3 PUFAs were evaluated for their effects on serum and brain lipids and on the three cytochrome P450 enzymes (CYPs 7A1, 27A1, and 46A1) that play key roles in cholesterol elimination from different organs. Hamsters on the highest concentration of n-3 PUFAs had a statistically significant decrease in LDL and HDL cholesterol and no change in serum total cholesterol and triglycerides levels. CYP27A1 and CYP46A1 mRNA levels were increased in the liver and brain, respectively, whereas possible effects on CYP7A1 were obscured by a marked intergroup variability at mRNA, protein and sterol product levels. Increased levels of CYP46A1 mRNA in the brain did not lead to significant changes in the levels of lathosterol, 24S-hydroxycholesterol or cholesterol in this organ. The data obtained are discussed in relation to inconsistent effects of n-3 PUFAs on serum lipids in human trials and reported positive effects of fish oil on cognitive function.

OBJECTIVE-Evaluate the expression and function of Catechol-O-methyltransferase (COMT) in human fetal membranes at term.METHODS-Fetal membranes obtained from women between 38 and 42 weeks of gestation, after 1) vaginal delivery with spontaneous labor and 2) pre-labor elective cesarean section (no-labor), were assayed for COMT expression using quantitative real time PCR, immuno-histochemistry and western blot analysis. Prostaglandin E 2 secretion from amnion and choriodecidua explants treated with or without COMT inhibitor was assayed by ELISA.RESULTS-Amnion layer of fetal membranes from laboring women expressed significantly higher levels of COMT, compared to those from women with no-labor. COMT was higher in the amnion layer than in choriodecidua. Selective COMT inhibition significantly decreased prostaglandin E 2 production from fetal membranes.CONCLUSION-Labor increasesCOMT expression in the amnion of human fetal membranes. Selective COMT inhibition decreased prostaglandinE 2 secretion in fetal explant cultures, suggesting a role for COMT in human labor and delivery.

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