Sequential induction of prostaglandin E and D synthases in inflammation

Enhanced biosynthesis of prostaglandin (PG)D2 and subsequent formation of 15-deoxy-Δ12,14-PGJ2 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)-1β in heart was enhanced 4 h 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 4 h after endotoxin administration, hematopoietic (H)-PGDS expression was enhanced only ⩾48 h after endotoxin. The expression of lipocalin-type (L)-PGDS was not significantly influenced. mRNA encoding the putative target of 15-deoxy-Δ12,14-PGJ2, peroxisome proliferator-activated receptor γ, was enhanced between 4 and 24 h after induction of inflammation. Treatment of mice with acetylsalicylic acid or indomethacin at doses effective to cause near-complete inhibition of PGE2 and PGD2 biosynthesis in heart ex vivo resulted in enhanced expression of IL-1β 24 h after endotoxin administration. These results provide additional support for the hypothesis of a shift towards PGD2 biosynthesis during resolution of inflammation.