The regulation of ciliary neurotrophic factor, leukemia inhibitory factor and monocyte chemoattractant protein-1 in injured peripheral nervous tissue /

Studies of Wallerian degeneration, the phenomenon wherein axons severed from the nerve cell body disintegrate, have revealed tightly regulated interactions between axons and Schwann cells. This present study focused on Schwann cell changes that occur following nerve injury. To tease out the different signals that influence the changes in Schwann cell phenotype, the regulation of three Schwann cell genes, namely ciliary neurotrophic factor (CNTF), leukemia inhibitory factor (LIF) and monocyte chemoattractant protein-1 (MCP-1), was investigated. Data showed that CNTF mRNA, regulated in a similar manner as myelin P 0, is induced by axonal contact even in the absence of transport from the nerve cell body. The mRNAs for LIF, which belongs to the same family as CNTF, and MCP-1 are induced in a biphasic manner in transected nerves---within 3--6 hours at the site of lesion and by 24 hours in the entire distal stump. Also, the induction of MCP-1 mRNA at the lesion site appears to be mediated by oxygen radicals. In vitro, Schwann cells produce MCP-1 mRNA in response to TNF-alpha stimulation through a pathway that can be inhibited by anti-oxidants and does not appear to require NF-kappaB activation. However, in vivo TNF-alpha is not crucial to the induction of MCP-1 mRNA in injured PNS. In contrast to the signal that decreases CNTF mRNA synthesis, the signals that induce MCP-1 and LIF mRNA are not strongly dependent on axonal degeneration