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~1α~ 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~1α~ 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~1α~ 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~1α~; but only in the presence of arachidonic acid. As observed for injured sciatic nerve, the production of PGE~2~ and 6‐keto‐PGF~1α~ 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~1α~ was unchanged. In contrast, macrophages treated with adult sciatic nerve homogenate did not produce significant amounts of either PGE~2~ or 6‐keto‐PGF~1α~ during the entire course of treatment. We conclude that injured sciatic nerves produce PGE~2~ and 6‐keto‐PGF~1α~ 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. Published 2004 Wiley‐Liss, Inc.