Cytokine-induced coordinate expression of enzymes of prostaglandin biosynthesis and metabolism: 15-hydroxyprostaglandin dehydrogenase.
The effects of pro-inflammatory cytokines on 15-hydroxyprostaglandin dehydrogenase (PGDH) expression and prostaglandin (PG) metabolizing activity were investigated in placental tissue. Treatment of trophoblast cells in primary culture with interleukin-1beta (IL-1beta) or tumour necrosis factor-alpha (TNF-alpha) resulted in decreased prostaglandin metabolizing activity. This was assessed both by determining the ratio of production of prostaglandins to their metabolites, and by Northern blot analysis of PGDH mRNA abundance. Dexamethasone had similar inhibitory effect. We hypothesize that proinflammatory cytokines act to enhance prostaglandin actions through coordinated effects on activities of enzymes of both prostaglandin biosynthesis and metabolism, perhaps in concert with effects on receptor function.
Mitchell
M D
MD
Department of Pharmacology and Clinical Pharmacology, Faculty of Medical and Health Sciences, The University of Auckland, New Zealand. m.mitchell@auckland.ac.nz
Goodwin
V
V
Mesnage
S
S
Keelan
J A
JA
D015152:Blotting, Northern; D002478:Cells, Cultured; D016207:Cytokines / Q000494:pharmacology*; D003907:Dexamethasone / Q000494:pharmacology; D015237:Dinoprost / Q000378:metabolism; D015232:Dinoprostone / Q000031:analogs & derivatives / Q000378:metabolism; D015870:Gene Expression / Q000187:drug effects*; D005938:Glucocorticoids / Q000494:pharmacology; D006911:Hydroxyprostaglandin Dehydrogenases / Q000235:genetics*; D007375:Interleukin-1 / Q000494:pharmacology; D010920:Placenta / Q000201:enzymology; D011453:Prostaglandins / Q000096:biosynthesis* / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D014327:Trophoblasts / Q000201:enzymology; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D016207:Cytokines; D005938:Glucocorticoids; D007375:Interleukin-1; D011453:Prostaglandins; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; C025087:15-keto-13,14-dihydroprostaglandin E2; D003907:Dexamethasone; D015237:Dinoprost; D006911:Hydroxyprostaglandin Dehydrogenases; C035859:15-hydroxyprostaglandin dehydrogenase; D015232:Dinoprostone