84 Abstracts

Inhibition of macrophage iNOS gene activation in the murine fetus, neonate, and placenta by docosahexaenoic acid (DHA) C.Y. Lu, M.L. Kielar, J.G. Penfield, S.C. Sicher, L. Che, A. Wall. Uniuer- sity of Texas, Southwestern Medical Centre, Dallas, TX 75235-8856, USA

We previously demonstrated profound deficits in macrophage activation during listeria infection of the murine placenta [J. Clin. Invest. (1987) 79, 1234; J. Immunol. (1988) 140, 38471. Such inhibition may reflect mecha- nisms which ordinarily prevent maternal anti-fetal immune responses. We recently demonstrated that DHA inhibits activation of the gene for in- ducible nitric oxide synthase (iNOS) [J. Exp. Med. (1996) 183, 12411. We studied DHA because serum concentrations in the fetus and neonate are 50 x those in the adult. We studied iNOS because this enzyme produces nitric oxide (NO) which is the ultimate effector in host defences against many pathogens and tumors. We found that DHA was the most inhibitory of the eight 20 and 22 carbon fatty acids tested. Although DHA is incorporated into membrane phospholipids, such incorporation was not required for inhibition. DHA was less inhibitory when macrophages incor- porated DHA prior to stimulation by IFNy and LPS, than when macrophages were simultaneously exposed to DHA and IFNy plus LPS. We found that NO is not produced until 10 h after macrophages are stimulated, and that DHA present only during this 10 h was inhibitory. We also found that DHA inhibited the increased abundance of iNOS mRNA by macrophages stimulated by IFN;) plus LPS. Nuclear run-on studies and promoter constructs containing 1500 bp of the 5’ flanking region of the iNOS gene ligated to CAT both demonstrated that inhibition occurred at the level of gene transcription. Finally we found that DHA did not inhibit the production of NO by macrophages which had previously been stimu- lated by IFN~J plus LPS, and whose iNOS was already producing NO. This suggested that DHA did not affect the enzymatic activity of iNOS.

Keywords: iNOS; Docosahexaenoic acid; Macrophage; Placenta

TNF-a production is reduced and IlcBa mRNA synthesis is enhanced by LPS-activated mouse macrophages exposed to progesterone in vitro Lance Miller, Joan S. Hunt. Departments of Pathology and Laboratory Medicine and Anatomy and Cell Biology, University of Kansas Medical Center, 3901 Rainbow Blvd., Kansas City, KS 66160-7410 USA

The female sex steroid hormones, estrogen and progesterone, exert both immunosuppressive and immunostimulatory effects on the complex process