Figure 4.

Biosynthesis of 15d-PGJ₂ in humans. (a) Varied impact of COX inhibition on PG metabolites and a auto-oxidative product of arachidonic acid. Urine collections were obtained before and after aspirin (81 mg/d × 6 days) as described in the Methods section. The effects of a COX inhibitor on 15d-PGJ₂ formation are compared with markers of COX-dependent (Tx-M and PGI-M) and COX-independent, free radical catalyzed isoprostane (8,12-iso-iPF_2α-VI). Tx-M = 2,3-dinor TxB₂. *P < 0.05. (b) COX-2 is the dominant source of 15d-PGJ₂ biosynthesis in humans. 15d-PGJ₂ levels in control volunteers (n = 21) were compared with those treated with the COX-2 selective NSAID celecoxib (n = 6) or nonselective ibuprofen (n = 5) (800 mg), administered acutely 30 minutes before urine collection. *P < 0.05; **P < 0.01. (c) Biosynthesis of PGI₂, but not 15d-PGJ₂, is altered during an acute inflammatory response in humans. Volunteers (n = 6) received LPS (4 ng/kg). PGI-M (2,3-dinor 6-keto-PGF_1α) was measured at multiple time points and is plotted as the mean ± SD (dotted line). For 15d-PGJ₂ measurements, urine was collected before LPS treatment (–2 to 0 hours) and at time points corresponding to peak inflammatory (4–6 hours) and resolution (16–24 hours) phases of response. Each individual is represented by a unique symbol that is conserved across time points. Median levels are indicated by horizontal lines. (d) Biosynthesis of 15d-PGJ₂ is unaltered in diabetes or obesity. 15d-PGJ₂ levels in healthy individuals are shown in comparison to obese (BMI ≥ 30) and nonobese (BMI < 30) patients with noninsulin-dependent type 2 diabetes. Median levels are indicated by horizontal lines.