Sequential induction of prostaglandin E and D synthases in inflammation.
Enhanced biosynthesis of prostaglandin (PG)D(2) and subsequent formation of 15-deoxy-Delta(12,14)-PGJ(2) has been suggested to contribute to resolution of inflammation. The primary aim of the present study in mouse heart was, therefore, to determine at the transcriptional level if there is sequential induction of PGE and PGD synthases (S) during inflammation. Expression of interleukin (IL)-1beta in heart was enhanced 4h after systemic inflammation and declined thereafter within 3-5 days to basal levels. In contrast to cyclooxygenase-2 and membrane-bound (m)-PGES-1, which both peaked 4h after endotoxin administration, hematopoietic (H)-PGDS expression was enhanced only >or=48h after endotoxin. The expression of lipocalin-type (L)-PGDS was not significantly influenced. mRNA encoding the putative target of 15-deoxy-Delta(12,14)-PGJ(2), peroxisome proliferator-activated receptor gamma, was enhanced between 4 and 24h after induction of inflammation. Treatment of mice with acetylsalicylic acid or indomethacin at doses effective to cause near-complete inhibition of PGE(2) and PGD(2) biosynthesis in heart ex vivo resulted in enhanced expression of IL-1beta 24h after endotoxin administration. These results provide additional support for the hypothesis of a shift towards PGD(2) biosynthesis during resolution of inflammation.
Schuligoi
Rufina
R
Institute for Experimental and Clinical Pharmacology, Medical University Graz, A-8010 Graz, Univ.-Platz 4, Austria. rufina.schuligoi@meduni-graz.at
Grill
Magdalena
M
Heinemann
Akos
A
Peskar
Bernhard A
BA
Amann
Rainer
R
D000818:Animals; D001483:Base Sequence; D051546:Cyclooxygenase 2; D017931:DNA Primers; D004790:Enzyme Induction; D007249:Inflammation / Q000201:enzymology*; D007375:Interleukin-1 / Q000235:genetics; D019746:Intramolecular Oxidoreductases / Q000096:biosynthesis*; D054834:Lipocalins; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009206:Myocardium / Q000201:enzymology / Q000378:metabolism; D047495:PPAR gamma / Q000235:genetics; D016133:Polymerase Chain Reaction; D000071876:Prostaglandin-E Synthases; D011451:Prostaglandin-Endoperoxide Synthases / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics
D017931:DNA Primers; D007375:Interleukin-1; D054834:Lipocalins; D047495:PPAR gamma; D012333:RNA, Messenger; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases; D019746:Intramolecular Oxidoreductases; C022466:prostaglandin R2 D-isomerase; D000071876:Prostaglandin-E Synthases