Cytokine-induced coordinate expression of enzymes of prostaglandin biosynthesis and metabolism: 15-hydroxyprostaglandin dehydrogenase

The effects of pro-inflammatory cytokines on 15-hydroxyprostaglandin dehydr ogenase (PGDH) expression and prostaglandin (PG) metabolizing activity were investigated in placental tissue. Treatment of trophoblast cells in primar y culture with interleukin-1 beta (IL-1 beta) or tumour necrosis factor-alp ha (TNF-alpha) resulted in decreased prostaglandin metabolizing activity. T his was assessed both by determining the ratio of production of prostagland ins to their metabolites, and by Northern blot analysis of PGDH mRNA abunda nce. Dexamethasone had similar inhibitory effect. We hypothesize that proin flammatory cytokines act to enhance prostaglandin actions through coordinat ed effects on activities of enzymes of both prostaglandin biosynthesis and metabolism, perhaps in concert with effects on receptor function. (C) 2000 Harcourt Publishers Ltd.