Effect of endotoxin treatment on the expression and localization of spinal cyclooxygenase, prostaglandin synthases, and PGD2 receptors

Systemic inflammation leads to increased expression of spinal cyclooxygenase (COX)-2 and to a subsequent increase of prostaglandin (PG) biosynthesis, which contribute to the development of hyperalgesia and allodynia. In this study, endotoxin caused a sequential induction of membrane bound prostaglandin E synthase-1 and lipocalin-type PGD synthase (L-PGDS) in the mouse spinal cord. L-PGDS expression was detected in the leptomeninges, oligodendrocytes, and interestingly, in discrete perivascular cells. Endotoxin-caused increase was most prominent in oligodendrocytes. Endotoxin-induced COX-2 and membrane bound prostaglandin E synthase-1 were restricted to the leptomeninges and perivascular cells. COX-1 was not influenced by endotoxin. We found COX-1 expressed in microglia, some of them in close proximity to L-PGDS-positive oligodendrocytes and co-localization of COX-1 with L-PGDS in perivascular and leptomeningeal cells under control conditions. It can be assumed, that PGD(2) biosynthesis under control conditions is mediated via COX-1 and that during inflammation, increased PGD(2) is dependent on COX-2. We found the PGD(2) receptors DP1 and chemoattractant receptor homologous molecule expressed on T helper type 2 cells (CRTH2) localized in neurons of the dorsal, and motoneurons in the ventral horn. The localization of the PGD2 receptors DP1 and CRTH in spinal cord neurons, particularly in neurons of lamina I and II involved in the processing of nociceptive stimuli, supports a role of PGD(2) under inflammatory conditions.