title: Prostaglandin E(2) and 6-keto-prostaglandin F(1alpha) production is elevated following traumatic injury to sciatic nerve.
abstract: Sciatic nerve explants cultured either alone or in the presence of peritoneal macrophages were used to study prostaglandin E(2) (PGE(2)) and 6-keto-PGF(1alpha) production following traumatic peripheral nerve injury. Although barely detectable at early time points (1-3 h in vitro), the production of PGE(2) and 6-keto-PGF(1alpha) by sciatic nerve explants increased significantly after 18 h and remained elevated for up to 96 h. The cyclooxygenase-2 (COX-2) selective inhibitor, NS-398, inhibited PGE(2) and 6-keto-PGF(1alpha) production by injured sciatic nerve in a dose-dependent manner. Consistent with the observed effect of NS-398, peripheral nerve explants, as well as Schwann cells and perineural fibroblasts cultured from neonatal sciatic nerve, each contained COX-2 immunoreactivity after 24 h in vitro. Both Schwann cells and perineural fibroblasts produced significant amounts of PGE(2) and 6-keto-PGF(1alpha); but only in the presence of arachidonic acid. As observed for injured sciatic nerve, the production of PGE(2) and 6-keto-PGF(1alpha) by primary Schwann cells and perineural fibroblasts was completely inhibited by NS-398. Compared to macrophages cultured alone, macrophages cultured in the presence of sciatic nerve explants produced large amounts of PGE(2), whereas the level of 6-keto-PGF(1alpha) was unchanged. In contrast, macrophages treated with adult sciatic nerve homogenate did not produce significant amounts of either PGE(2) or 6-keto-PGF(1alpha) during the entire course of treatment. We conclude that injured sciatic nerves produce PGE(2) and 6-keto-PGF(1alpha) by a mechanism involving COX-2 activity and that macrophages produce large amounts of PGE(2) in response to soluble factors produced by injured nerve but not during the phagocytosis of peripheral nerve debris.
authors.affiliation: Neuroscience Graduate Program, Neurobiology, and Anatomy Loyola University of Chicago, Maywood, Illinois, USA.
authors.forename: Naser
authors.initials: N
authors.lastname: Muja
authors.forename: George H
authors.initials: GH
authors.lastname: DeVries
mesh_terms: D015121:6-Ketoprostaglandin F1 alpha / Q000378:metabolism*; D000818:Animals; D002478:Cells, Cultured; D017077:Culture Media, Conditioned / Q000494:pharmacology; D051546:Cyclooxygenase 2; D015232:Dinoprostone / Q000378:metabolism*; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism; D066298:In Vitro Techniques; D007527:Isoenzymes / Q000378:metabolism; D008264:Macrophages / Q000166:cytology / Q000378:metabolism; D010587:Phagocytosis / Q000502:physiology; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012583:Schwann Cells / Q000166:cytology / Q000378:metabolism; D012584:Sciatic Nerve / Q000166:cytology / Q000293:injuries* / Q000378:metabolism*; D012995:Solubility
chemical_list: D017077:Culture Media, Conditioned; D007527:Isoenzymes; D015121:6-Ketoprostaglandin F1 alpha; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases; D015232:Dinoprostone