TUMOR-NECROSIS-FACTOR-ALPHA AND INTERLEUKIN-1-BETA INHIBIT THE SYNTHESIS AND RELEASE OF RENIN FROM HUMAN DECIDUAL CELLS

Cytokines modulate hormone expression in many cell types, including th e expression of renin in juxtaglomerular cells. However, the effect of cytokines on the expression of renin from extrarenal cells is unknown . In this paper, we have examined whether tumor necrosis factor-alpha (TNF alpha) and interleukin-1 beta (IL-1 beta) modulate the release of renin from human decidual cells. Continuous exposure of primary decid ual cell cultures from term pregnancies to TNF alpha and IL-1 beta cau sed dose-dependent inhibition of renin release. The maximal inhibition s by TNF alpha and IL-1 beta were 75.5% and 55.2%, respectively, and t he half-maximal effective doses of TNF alpha and IL-1 beta were 30 and 1.1 pmol/L, respectively. The decrease in renin release by the cytoki nes was statistically significant on days 2-5 (P > 0.001 at each time) and was accompanied by inhibition of renin synthesis and renin messen ger ribonucleic acid levels. The renin messenger ribonucleic acid leve ls in cells exposed for 4 days to TNF alpha(50 ng/mL) or IL-1 beta (50 pg/mL) were 58.0% and 37.7% less than those in control cells, respect ively. As decidual macrophages express TNF alpha and IL-1 beta, the re sults of this study strongly suggest a paracrine role for cytokines in the regulation of decidual renin expression. The effect of these cyto kines on renin expression in decidual cells is opposite that in juxtag lomerular cells.